Clinical, Genetic and Environmental Factors Associated with Congenital Vertebral Malformations

PubMed Central

Giampietro, P.F.; Raggio, C.L.; Blank, R.D.; McCarty, C.; Broeckel, U.; Pickart, M.A.

2013-01-01

Congenital vertebral malformations (CVM) pose a significant health problem because they can be associated with spinal deformities, such as congenital scoliosis and kyphosis, in addition to various syndromes and other congenital malformations. Additional information remains to be learned regarding the natural history of congenital scoliosis and related health problems. Although significant progress has been made in understanding the process of somite formation, which gives rise to vertebral bodies, there is a wide gap in our understanding of how genetic factors contribute to CVM development. Maternal diabetes during pregnancy most commonly contributes to the occurrence of CVM, followed by other factors such as hypoxia and anticonvulsant medications. This review highlights several emerging clinical issues related to CVM, including pulmonary and orthopedic outcome in congenital scoliosis. Recent breakthroughs in genetics related to gene and environment interactions associated with CVM development are discussed. The Klippel-Feil syndrome which is associated with cervical segmentation abnormalities is illustrated as an example in which animal models, such as the zebrafish, can be utilized to provide functional evidence of pathogenicity of identified mutations. PMID:23653580

[Sirenomelia].

PubMed

García, J; Romero-Araus, J

1996-09-01

Sirenomelia is an uncommon congenital malformation of unknown etiology characterized by all degrees of severity in merning, malrotation, and dysgenesis of the lower limbs, combining as it does malformation with several anomalies of the external and internal organs, specially of the urogenital and gastrointestinal systems and other lumbosacral vertebral abnormalities; the severity of the associated malformations are not compatible with life. A genetic mechanism leading to sirenomelia is unlikely, due to the absence of the familial cases.

Evaluation of radiography as a screening method for detection and characterisation of congenital vertebral malformations in dogs.

PubMed

Brocal, Josep; De Decker, Steven; José-López, Roberto; Guevar, Julien; Ortega, Maria; Parkin, Tim; Ter Haar, Gert; Gutierrez-Quintana, Rodrigo

2018-05-19

Congenital vertebral malformations (CVM) are common in brachycephalic 'screw-tailed' dogs; they can be associated with neurological deficits and a genetic predisposition has been suggested. The purpose of this study was to evaluate radiography as a screening method for congenital thoracic vertebral malformations in brachycephalic 'screw-tailed' dogs by comparing it with CT. Forty-nine dogs that had both radiographic and CT evaluations of the thoracic vertebral column were included. Three observers retrospectively reviewed the images independently to detect CVMs. When identified, they were classified according to a previously published radiographic classification scheme. A CT consensus was then reached. All observers identified significantly more affected vertebrae when evaluating orthogonal radiographic views compared with lateral views alone; and more affected vertebrae with the CT consensus compared with orthogonal radiographic views. Given the high number of CVMs per dog, the number of dogs classified as being CVM free was not significantly different between CT and radiography. Significantly more midline closure defects were also identified with CT compared with radiography. Malformations classified as symmetrical or ventral hypoplasias on radiography were frequently classified as ventral and medial aplasias on CT images. Our results support that CT is better than radiography for the classification of CVMs and this will be important when further evidence of which are the most clinically relevant CVMs is identified. These findings are of particular importance for designing screening schemes of CVMs that could help selective breeding programmes based on phenotype and future studies. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Advances in congenital vertebral malformation caused by genomic copy number variation].

PubMed

Liu, Zhenlei; Wu, Nan; Wu, Zhihong; Zuo, Yuzhi; Qiu, Guixing

2016-04-01

Congenital vertebral malformation (CVM) is a congenital vertebral structural deformity caused by abnormal somitogenesis during embryonic development, of which the reason lies in gene mutation or abnormal regulation of the genes that coordinate somitogenesis during embryonic period. ICVAS had proposed a new classification algorithm for CVM, which facilitated exploration for its genetic etiology. Genomic Copy Number Variation (CNV) is a kind of DNA mutation, which is important for human evolution, phenotype polymorphism and diseases. Series of advances have been made on genetic causes of CVM, especially on CVM caused by CNV. CNVs of chromosome 16p11.2, 10q24.31, 17p11.2, 20p11, 22q11.2 and a few other regions are associated with CVM, indicating that gene dosage may play important roles in the development of the spinal cord.

MICROCOMPUTED TOMOGRAPHIC, MORPHOMETRIC, AND HISTOPATHOLOGIC ASSESSMENT OF CONGENITAL BONE MALFORMATIONS IN TWO NEOTROPICAL VIPERIDS.

PubMed

de Carvalho, Marcelo Pires Nogueira; Sant'Anna, Sávio Stefanini; Grego, Kathleen Fernandes; de Campos Fonseca-Pinto, Ana Carolina Brandão; Lorigados, Carla Aparecida Batista; Queiroz-Hazarbassanov, Nicolle Gilda Teixeira; Catão-Dias, José Luiz

2017-10-01

Congenital malformations have been reported in all classes of vertebrates and may be a determinant of life span and survival. In reptiles, the incidence of congenital malformations can be associated with genetic and environmental causes, including pollution. The characterization of pathological processes involved in the development of congenital malformations of bone in snakes is rare in the literature, but is of great relevance in the field of reptile conservation and environmental health. We describe congenital bone lesions in 50 newborn jararaca (Bothrops jararaca) and 26 South American rattlesnakes (Crotalus durissus terrificus) born from wild-caught pregnant females in Southeastern Brazil. Lesions were evaluated by morphometric quantitative analysis, x-ray microtomography, and histopathologic descriptive analysis. Morphometric analysis showed that jararaca presented more severe axial lesions (kyphosis, scoliosis, and kyphoscoliosis) than rattlesnakes. Female rattlesnakes presented more severe axial lesions than did males. In rattlesnakes, spinal deformities were more frequently diagnosed in the caudal segment of the body. We present x-ray microtomographic assessments and images of malformed snakes (n=9) and characterized novel malformations, such as the agenesis of frontal, parietal, and supraoccipital bones in a jararaca specimen. Histopathologic findings included vertebral body fusion, myositis, coagulation necrosis, and disorganization of periaxial muscle fibers. The new methods and results presented in this study will be useful and informative for future research in pathology, teratology, embryology, and ecotoxicology in snakes.

Surgical management of Chiari I malformation based on different cerebrospinal fluid flow patterns at the cranial-vertebral junction.

PubMed

Fan, Tao; Zhao, HaiJun; Zhao, XinGang; Liang, Cong; Wang, YinQian; Gai, QiFei

2017-10-01

Chiari I malformation has been shown to present different cerebrospinal fluid (CSF) flow patterns at the cranial-vertebral junction (CVJ). Posterior fossa decompression is the first-line treatment for symptomatic Chiari I malformation. However, there is still controversy on the indication and selection of decompression procedures. This research aims to investigate the clinical indications, outcomes, and complications of the decompression procedures as alternative treatments for Chiari I malformation, based on the different CSF flow patterns at the cranial-vertebral junction. In this study, 126 Chiari I malformation patients treated with the two decompression procedures were analyzed. According to the preoperative findings obtained by using cine phase-contrast MRI (cine PC-MRI), the abnormal CSF flow dynamics at the CVJ in Chiari I malformation was classified into three patterns. After a preoperative evaluation and an intraoperative ultrasound after craniectomy, the two procedures were alternatively selected to treat the Chiari I malformation. The indication and selection of the two surgical procedures, as well as their outcomes and complications, are reported in detail in this work. Forty-eight patients underwent subdural decompression (SDD), and 78 received subarachnoid manipulation (SAM). Ninety patients were diagnosed as having Chiari I malformation with a syrinx. Two weeks after the operation, the modified Japanese Orthopedic Association (mJOA) scores increased from the preoperative value of 10.67 ± 1.61 to 12.74 ± 2.01 (P < 0.01). The mean duration of follow-up was 24.8 months; the mJOA scores increased from the postoperative value of 12.74 ± 2.01 to 12.79 ± 1.91 at the end of follow-up (P = 0.48). More complications occurred in the patients who underwent SAM than in those who received SDD (SAM 11 of 78 (9.5%) vs SDD 2 of 48 (3.5%)). The abnormal CSF flow dynamics at the CVJ in Chiari I malformation can be classified into three patterns. A SAM procedure is more feasible in Chiari I malformation (CM1) patients with pattern III CSF flow dynamics, whereas a SDD procedure is more suitable for CM1 patients with pattern I CSF flow dynamics. In CM1 patients with pattern II CSF flow dynamics, an intraoperative ultrasound after craniectomy could play an important role in the selection of an effective decompression procedure.

METHANOL EXPOSURE DURING GASTRULATION CAUSES HOLOPROSENCEPHALY, FACIAL DYSGENESIS AND CERVICAL VERTEBRAL MALFORMATIONS IN C57BL/6J MICE

EPA Science Inventory

Exposure of pregnant CD-1 mice to methanol during the period of gastrulation results in exencephaly, cleft palate, and cervical vertebra malformations (Rogers and Mole, 1997, Teratology 55, 364). C57BL/6J mice are sensitive to the teratogenicity of ethanol; fetuses of this strai...

[A vertebral arteriovenous fistula diagnosed by auscultation].

PubMed

Iglesias Escalera, G; Diaz-Delgado Peñas, R; Carrasco Marina, M Ll; Maraña Perez, A; Ialeggio, D

2015-01-01

Cervical artery fistulas are rare arteriovenous malformations. The etiology of the vertebral arteriovenous fistulas (AVF) can be traumatic or spontaneous. They tend to be asymptomatic or palpation or continuous vibration in the cervical region. An arteriography is necessary for a definitive diagnosis. The treatment is complete embolization of the fistula. We present the case of a two year-old male, where the mother described it «like a washing machine in his head». On palpation during the physical examination, there was a continuous vibration, and a continuous murmur in left cervical region. A vascular malformation in vertebral region was clinically suspected, and confirmed with angio-MRI and arteriography. AVF are rare in childhood. They should be suspected in the presence of noises, palpation or continuous vibration in the cervical region. Early diagnosis can prevent severe complications in asymptomatic children. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Initial evaluation of developmental malformation as an end point in mixture toxicity hazard assessment for aquatic vertebrates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dawson, D.A.; Wilke, T.S.

1991-04-01

The joint toxic action of three binary mixtures was determined for the embryo malformation endpoint of the aquatic FETAX (frog embryo teratogenesis assay: Xenopus) test system. Osteolathyrogenic compounds and short-chain carboxylic acids, representing separate, distinct modes of action for induction of malformation, were selected for testing in 96-hr, static-renewal tests. Three mixtures were tested for each combination, with each combination being tested on three separate occasions. Using toxic unit analysis, the combination of osteolathyrogens and the combination of carboxylic acids produced strictly additive (concentration addition) rates of malformation, while the combination of an osteolathyrogen and a carboxylic acid was less-than-additivemore » (response addition) for induction of malformation. Therefore, developmental malformation may have value as an endpoint in mixture toxicity hazard assessment.« less

Postnatal investigation of prenatally induced effects on the vertebral column of rats reduces the uncertainty of classification of anomalies.

PubMed

Chahoud, I; Talsness, C E; Walter, A; Grote, K

2015-12-01

Classification of substances as teratogenic is based on the observation of external, visceral and skeletal anomalies. Characterization of anomalies as variation or malformation is contingent upon their postnatal persistence and adversity to health. Lack of information thereof may result in inconsistent or incorrect classification. The aim of this work is the examination of vertebral skeletal anomalies regarding their postnatal fate on PNDs 7 and 21. The anomalies unossified, asymmetric ossification, bipartite ossification, hemicentric, as well as misshapen, did not persist up to PND21 and should be classified as a variation. The finding, cervical vertebra centrum dumbbell-shaped, should be categorized as a malformation due to its continued presence on PND 21. Lumbar centrum supernumerary sinister/dexter/sinister+dexter should also be classified as a malformation. This study demonstrates that postnatal examination is useful and substantially improves the ability to perform a scientifically sound classification of an anomaly compared to investigations terminated on GD 21. Copyright © 2015 Elsevier Inc. All rights reserved.

Congenital Auricular Malformations: Description of Anomalies and Syndromes.

PubMed

Bartel-Friedrich, Sylva

2015-12-01

Half of the malformations in the ear, nose, and throat region affect the ear. Malformations of the external ear (pinna or auricle with external auditory canal [EAC]) are collectively termed microtia. Microtia is a congenital anomaly that ranges in severity from mild structural abnormalities to complete absence of the external ear (anotia). Microtia occurs more frequently in males (∼2 or 3:1), is predominantly unilateral (∼70-90%), and more often involves the right ear (∼60%). The reported prevalence varies geographically from 0.83 to 17.4 per 10,000 births. Microtia may be genetic (with family history, spontaneous mutations) or acquired. Malformations of the external ear can also involve the middle ear and/or inner ear. Microtia may be an isolated birth defect, but associated anomalies or syndromes are described in 20 to 60% of cases, depending on study design. These generally fit within the oculo-auriculo-vertebral spectrum; defects are located most frequently in the facial skeleton, facial soft tissues, heart, and vertebral column, or comprise a syndrome (e.g., Treacher Collins syndrome). Diagnostic investigation of microtia includes clinical examination, audiologic testing, genetic analysis and, especially in higher grade malformations with EAC deformities, computed tomography (CT) or cone-beam CT for the planning of surgery and rehabilitation procedures, including implantation of hearing aids. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Magnetic resonance imaging features of complex Chiari malformation variant of Chiari 1 malformation.

PubMed

Moore, Hannah E; Moore, Kevin R

2014-11-01

Complex Chiari malformation is a subgroup of Chiari 1 malformation with distinct imaging features. Children with complex Chiari malformation are reported to have a more severe clinical phenotype and sometimes require more extensive surgical treatment than those with uncomplicated Chiari 1 malformation. We describe reported MR imaging features of complex Chiari malformation and evaluate the utility of craniometric parameters and qualitative anatomical observations for distinguishing complex Chiari malformation from uncomplicated Chiari 1 malformation. We conducted a retrospective search of the institutional imaging database using the keywords "Chiari" and "Chiari 1" to identify children imaged during the 2006-2011 time period. Children with Chiari 2 malformation were excluded after imaging review. We used the first available diagnostic brain or cervical spine MR study for data measurement. Standard measurements and observations were made of obex level (mm), cerebellar tonsillar descent (mm), perpendicular distance to basion-C2 line (pB-C2, mm), craniocervical angle (degrees), clivus length, and presence or absence of syringohydromyelia, basilar invagination and congenital craniovertebral junction osseous anomalies. After imaging review, we accessed the institutional health care clinical database to determine whether each subject clinically met criteria for Chiari 1 malformation or complex Chiari malformation. Obex level and craniocervical angle measurements showed statistically significant differences between the populations with complex Chiari malformation and uncomplicated Chiari 1 malformation. Cerebellar tonsillar descent and perpendicular distance to basion-C2 line measurements trended toward but did not meet statistical significance. Odontoid retroflexion, craniovertebral junction osseous anomalies, and syringohydromyelia were all observed proportionally more often in children with complex Chiari malformation than in those with Chiari 1 malformation. Characteristic imaging features of complex Chiari malformation, especially obex level, permit its distinction from the more common uncomplicated Chiari 1 malformation.

A Novel Cardiotoxic Mechanism for a Pervasive Global Pollutant

NASA Astrophysics Data System (ADS)

Brette, Fabien; Shiels, Holly A.; Galli, Gina L. J.; Cros, Caroline; Incardona, John P.; Scholz, Nathaniel L.; Block, Barbara A.

2017-01-01

The Deepwater Horizon disaster drew global attention to the toxicity of crude oil and the potential for adverse health effects amongst marine life and spill responders in the northern Gulf of Mexico. The blowout released complex mixtures of polycyclic aromatic hydrocarbons (PAHs) into critical pelagic spawning habitats for tunas, billfishes, and other ecologically important top predators. Crude oil disrupts cardiac function and has been associated with heart malformations in developing fish. However, the precise identity of cardiotoxic PAHs, and the mechanisms underlying contractile dysfunction are not known. Here we show that phenanthrene, a PAH with a benzene 3-ring structure, is the key moiety disrupting the physiology of heart muscle cells. Phenanthrene is a ubiquitous pollutant in water and air, and the cellular targets for this compound are highly conserved across vertebrates. Our findings therefore suggest that phenanthrene may be a major worldwide cause of vertebrate cardiac dysfunction.

Vertebral hemangiomas in the thoracic spine of multiple sclerosis patients are connected with fewer demyelinating lesions at the same level. Possible impact on pathophysiology and clinical course.

PubMed

Anagnostouli, Maria; Katsavos, Serafeim; Kyrozis, Andreas; Gontika, Maria; Voumvourakis, Konstantinos I; Kapaki, Elisabeth

2016-08-01

Mechanisms of angiogenesis regulate multiple sclerosis (MS) lesions' evolution, displaying both neuroprotective and harmful effects. Factors traditionally considered as purely angiogenic, like vascular endothelial growth factor (VEGF), exert complex heterogenous actions on both neural and vascular malformation-derived tissues. Aim of this retrospective study was to examine, for the first time, potential associations between the presence of common vascular malformations, like vertebral hemangiomas (VHs), and several clinico-radiological MS parameters. 236 MS patients who were followed in our Outpatient Clinic were recruited in this study. Outcome measures concerned demographics, disease-derived variables, and MS-lesions' distribution in VHs - positive and negative patients. All data were collected retrospectively. Potential correlations were assessed with univariate statistical analyses (p = 0.05), followed by multivariate regression models, for purposes of confounder-effects elimination. VH presence showed significant negative correlations with presence of MS lesions in the thoracic (p = 0.005 for thoracic VHs), but not the cervical cord. Trends towards negative associations of VH presence with subtentorial MS lesions and positive family history for MS were also observed. Our observations suggest that VH presence may reduce the risk of thoracic demyelinating lesions in MS patients. They could be explained as part of a multifaceted angiogenic process, concomitantly enhancing neural repair and abnormal hemangioma vascularization.

Missing Links Between Genetically Inherited Molecules in Split Cord Malformation and Other Anomaly: A Bench to Bedside Approach

PubMed Central

Barik, Mayadhar; Mishra, Pravash R.; Mohapatra, Ashok Kumar

2018-01-01

Aim: Split cord malformation (SCM) is associated with extensive vertebral fusions (Klippel–Feil anomaly). In light of previous embryological theories and recent research findings, we attempt to document the origin of split cord, and vertebral fusions involvement of spectrum of genes is necessary to know better the etiopathogenesis of SCM and its associated diseases. Materials and Methods: We used the various databases such as PubMed/MEDLINE, Cochrane Review, Hinari, and Google Scholar for the recently published medical literature. The women had been living and still born infants had SCM. The relative risk (RR) and possible molecular mechanism are described details of major genes and its variants in details. Although molecular genetics involvement including with recent advances of study add an evidence of both Mendelian and Non-Mendelian fashion is discussed with all genetic components. We mentioned our earlier experience and responsibility of SCM and its associated diseases. Results: Although different mechanisms are suggested for the development of SCM observed in our experience, there is a midline lesion bisecting the neuroepithelium and the notochordal plate, which is responsible for complete splitting of the cervical cord with anterior bony defect. The localized disturbance of cervical neural tube closure accounts for SCM with partial dorsal splitting of the cord with posterior vertebral defect and associated diseases. Conclusions: According to the best of our knowledge, this report is the first one to be documented by wider spectrum of variants from (experimental studies to human subject). This add a complex interaction of mutant variants drive toward an additional second-hit alterations for the SCM. The up-to-date information, documented in proper order, derived the bench-to-bedside approach to overcome this burden of SCM, which is globally noticed with other additional diseases. PMID:29899771

Missing Links Between Genetically Inherited Molecules in Split Cord Malformation and Other Anomaly: A Bench to Bedside Approach.

PubMed

Barik, Mayadhar; Mishra, Pravash R; Mohapatra, Ashok Kumar

2018-01-01

Split cord malformation (SCM) is associated with extensive vertebral fusions (Klippel-Feil anomaly). In light of previous embryological theories and recent research findings, we attempt to document the origin of split cord, and vertebral fusions involvement of spectrum of genes is necessary to know better the etiopathogenesis of SCM and its associated diseases. We used the various databases such as PubMed/MEDLINE, Cochrane Review, Hinari, and Google Scholar for the recently published medical literature. The women had been living and still born infants had SCM. The relative risk (RR) and possible molecular mechanism are described details of major genes and its variants in details. Although molecular genetics involvement including with recent advances of study add an evidence of both Mendelian and Non-Mendelian fashion is discussed with all genetic components. We mentioned our earlier experience and responsibility of SCM and its associated diseases. Although different mechanisms are suggested for the development of SCM observed in our experience, there is a midline lesion bisecting the neuroepithelium and the notochordal plate, which is responsible for complete splitting of the cervical cord with anterior bony defect. The localized disturbance of cervical neural tube closure accounts for SCM with partial dorsal splitting of the cord with posterior vertebral defect and associated diseases. According to the best of our knowledge, this report is the first one to be documented by wider spectrum of variants from (experimental studies to human subject). This add a complex interaction of mutant variants drive toward an additional second-hit alterations for the SCM. The up-to-date information, documented in proper order, derived the bench-to-bedside approach to overcome this burden of SCM, which is globally noticed with other additional diseases.

Ethanol teratogenesis in the C57BL/6J, DBA/2J, and A/J inbred mouse strains.

PubMed

Boehm, S L; Lundahl, K R; Caldwell, J; Gilliam, D M

1997-01-01

Research has shown variations in susceptibility to alcohol-related birth defects in humans. Genetic differences are one reason for this variability. This study compared three inbred mouse strains to determine whether they differ in their susceptibilities to ethanol teratogenesis because previous studies have generated conflicting data. Pregnant C57BL/6J (B6), DBA/2J (D2), and A/J (A) dams were intubated intragastrically with either an acute dose of ethanol (5.8 g/kg) or an isocaloric amount of maltose-dextrine on day 9 of pregnancy. Litters were removed on day 18 of pregnancy and examined for gross, soft-tissue, and skeletal malformations. Results showed that ethanol-exposed B6 litters had a higher percentage of digit (19%), kidney (24%), and skeletal (32%, mostly vertebral) malformations than their maltose-exposed controls (7% or below). Prenatal exposure to ethanol increased skeletal (68%, both rib and vertebral) malformations for A litters when compared to their maltose-exposed controls (4%), but did not increase digit or kidney malformations. Ethanol-exposed D2 litters did not differ from maltose-exposed controls. Maternal blood ethanol levels did not differ among the B6, D2, and A strains. These results provide additional evidence suggesting a genetic component to ethanol teratogenesis.

Prenatal development of the normal human vertebral corpora in different segments of the spine.

PubMed

Nolting, D; Hansen, B F; Keeling, J; Kjaer, I

1998-11-01

Vertebral columns from 13 normal human fetuses (10-24 weeks of gestation) that had aborted spontaneously were investigated as part of the legal autopsy procedure. The investigation included spinal cord analysis. To analyze the formation of the normal human vertebral corpora along the spine, including the early location and disappearance of the notochord. Reference material on the development of the normal human vertebral corpora is needed for interpretation of published observations on prenatal malformations in the spine, which include observations of various types of malformation (anencephaly, spina bifida) and various genotypes (trisomy 18, 21 and 13, as well as triploidy). The vertebral columns were studied by using radiography (Faxitron X-ray apparatus, Faxitron Model 43,855, Hewlett Packard) in lateral, frontal, and axial views and histology (decalcification, followed by toluidine blue and alcian blue staining) in and axial view. Immunohistochemical marking with Keratin Wide Spectrum also was done. Notochordal tissue (positive on marking with Keratin Wide Spectrum [DAKO, Denmark]) was located anterior to the cartilaginous body center in the youngest fetuses. The process of disintegration of the notochord and the morphology of the osseous vertebral corpora in the lumbosacral, thoracic, and cervical segments are described. Marked differences appeared in axial views, which were verified on horizontal histologic sections. Also, the increase in size was different in the different segments, being most pronounced in the thoracic and upper lumbar bodies. The lower thoracic bodies were the first to ossify. The morphologic changes observed by radiography were verified histologically. In this study, normal prenatal standards were established for the early development of the vertebral column. These standards can be used in the future--for evaluation of pathologic deviations in the human vertebral column in the second trimester.

Diprosopus with associated malformations: report of two cases.

PubMed

Pavone, L; Camera, G; Grasso, S; Gambini, C; Barberis, M; Garaffo, S; Russo, S

1987-09-01

We report on two patients with craniofacial duplication and anencephaly. In addition to these anomalies, one patient showed vertebral fusion and diaphragmatic hernia, and the other one presented cheilognathopalatoschisis.

Analysis of Lethality and Malformations During Zebrafish (Danio rerio) Development.

PubMed

Raghunath, Azhwar; Perumal, Ekambaram

2018-01-01

The versatility offered by zebrafish (Danio rerio) makes it a powerful and an attractive vertebrate model in developmental toxicity and teratogenicity assays. Apart from the newly introduced chemicals as drugs, xenobiotics also induce abnormal developmental abnormalities and congenital malformations in living organisms. Over the recent decades, zebrafish embryo/larva has emerged as a potential tool to test teratogenicity potential of these chemicals. Zebrafish responds to compounds as mammals do as they share similarities in their development, metabolism, physiology, and signaling pathways with that of mammals. The methodology used by the different scientists varies enormously in the zebrafish embryotoxicity test. In this chapter, we present methods to assess lethality and malformations during zebrafish development. We propose two major malformations scoring systems: binomial and relative morphological scoring systems to assess the malformations in zebrafish embryos/larvae. Based on the scoring of the malformations, the test compound can be classified as a teratogen or a nonteratogen and its teratogenic potential is evaluated.

[Osteological development of the vertebral column and caudal complex of Lujanus guttatus (Perciformes: Lutjanidae) larvae under rearing conditions].

PubMed

Rodríguez-Ibarra, Luz Estela; Abdo-de la Parra, María Isabel; Aguilar-Zárate, Gabriela; Valasco-Blanco, Gabriela; Ibarra-Castro, Leonardo

2015-03-01

The spotted rose snapper (Lutjanus guttatus) is an important commercial species in Mexico with good culture potential. The osteological study at early stages in this species is an important tool to confirm normal bone structure and for the detection of malformations that may occur during early development. This study was carried out in order to evaluate and describe the normal osteological development of the vertebral column and caudal complex of this species grown under controlled conditions. For this, a total of 540 larvae of L. guttatus, between 2.1 and 17.5 mm of total length (TL), were cultured during 36 days; culture conditions were 28 degrees C, 5.74 mg/L oxygen and 32.2 ups salinity with standard feeding rates. To detect growth changes, a sample of 15 organisms was daily taken from day one until day 36 of post-hatch (DPH). Samples were processed following standard techniques of clearing, and cartilage (alcian blue) and bone staining (alizarin red). Results showed that the vertebral column is composed of ten vertebrae in the abdominal region, and 14 vertebrae including the urostyle in the caudal region. The development of the axial skeleton starts with the neural arches and haemal arches at 3.8 mm TL. Caudal elements such as the hypurals and parahypural began to develop at 4.1 mm TL. Pre-flexion and flexion of the notochord and the formation of all hypurals were observed between 5.3 and 5.8 mm TL. Ossification of the vertebrae in the abdominal region and in some neural arches initiated at 9.5mm TL. In the caudal region, all the neural and haemal arches ossified at 10.2 mm TL. All the abdominal vertebrae and their respective neural arches and parapophyses ossified at 11.2 mm TL, while the elements of the caudal complex that ossified were the hypurals, parahypurals and modified haemal spines. All caudal fm rays, 12 neural spines and 3 haemal arches were ossified by 15.5 mm. The complete ossification process of this specie under laboratory culture conditions was observed when larvae reached 17.3 mm TL on 36 DPH. Detailed analysis of the osteological structures will allow a reference description to evaluate and detect malformations that may occur during the larval culture of the spotted rose snapper.

Sulphated glycosaminoglycans and proteoglycans in the developing vertebral column of juvenile Atlantic salmon (Salmo salar).

PubMed

Hannesson, Kirsten O; Ytteborg, Elisabeth; Takle, Harald; Enersen, Grethe; Bæverfjord, Grete; Pedersen, Mona E

2015-08-01

In the present study, the distribution of sulphated glycosaminoglycans (GAGs) in the developing vertebral column of Atlantic salmon (Salmo salar) at 700, 900, 1100 and 1400 d° was examined by light microscopy. The mineralization pattern was outlined by Alizarin red S and soft structures by Alcian blue. The temporal and spatial distribution patterns of different types of GAGs: chondroitin-4-sulphate/dermatan sulphate, chondroitin-6-sulphate, chondroitin-0-sulphate and keratan sulphate were addressed by immunohistochemistry using monoclonal antibodies against the different GAGs. The specific pattern obtained with the different antibodies suggests a unique role of the different GAG types in pattern formation and mineralization. In addition, the distribution of the different GAG types in normal and malformed vertebral columns from 15 g salmon was compared. A changed expression pattern of GAGs was found in the malformed vertebrae, indicating the involvement of these molecules during the pathogenesis. The molecular size of proteoglycans (PGs) in the vertebrae carrying GAGs was analysed with western blotting, and mRNA transcription of the PGs aggrecan, decorin, biglycan, fibromodulin and lumican by real-time qPCR. Our study reveals the importance of GAGs in development of vertebral column also in Atlantic salmon and indicates that a more comprehensive approach is necessary to completely understand the processes involved.

[Nuclear magnetic resonance of anorectal malformations and persistent postoperative fecal incontinence].

PubMed

de Agustín, J C; Alami, H; Lassaletta, L; Gámez, M; Fernández, A; Fraile, E; Alenda, J G; Rollán, V; Utrilla, J G

1992-07-01

We review our experience with Magnetic Resonance Imaging (MRI) in the evaluation of 6 patients showing anorectal malformation, and 4 more with persistent postoperative fecal incontinence. Preoperative sagittal, axial and coronal planes were studied with special consideration to the pelvic and vertebral structures. The excellent resolution of MRI allowed accurate identification of the pelvic musculature in all patients, including those with bizarre sacral abnormalities. MRI revealed structural anomalies not detected previously, such as teathering cord, intraspinal lipoma, presacral mass and renal malformation. In our institution, MRI has replaced the CT scan in the study of patients suffering of persistent fecal incontinence. In non operated on cases of anorectal malformations, MRI determines with extraordinary accuracy the location of the rectal atretic pouch, the actual pelvic muscular quality, and the detection of previously unsuspected associated anomalies.

Jarcho-Levin syndrome presenting with diaphragmatic hernia.

PubMed

Onay, O S; Kinik, S T; Otgün, Y; Arda, I S; Varan, B

2008-08-01

Jarcho-Levin syndrome (spondylothoracic or spondylocostal dysostosis) is an eponym that is used to define individuals with a short neck, short trunk, and short stature and multiple vertebral anomalies. The prognosis is directly related to respiratory complications. Reported findings associated with Jarcho-Levin syndrome include congenital heart defects, abdominal wall malformations, genitourinary malformations, upper limb anomalies, and neural tube defects. We report on a 6-day-old girl who presented with an incomplete form of Jarcho-Levin syndrome with late-presenting congenital diaphragmatic hernia and congenital heart disease.

ptk7 mutant zebrafish models of congenital and idiopathic scoliosis implicate dysregulated Wnt signalling in disease

PubMed Central

Hayes, Madeline; Gao, Xiaochong; Yu, Lisa X; Paria, Nandina; Henkelman, R. Mark; Wise, Carol A.; Ciruna, Brian

2014-01-01

Scoliosis is a complex genetic disorder of the musculoskeletal system, characterized by three-dimensional rotation of the spine. Curvatures caused by malformed vertebrae (congenital scoliosis (CS)) are apparent at birth. Spinal curvatures with no underlying vertebral abnormality (idiopathic scoliosis (IS)) most commonly manifest during adolescence. The genetic and biological mechanisms responsible for IS remain poorly understood due largely to limited experimental models. Here we describe zygotic ptk7 (Zptk7) mutant zebrafish, deficient in a critical regulator of Wnt signalling, as the first genetically defined developmental model of IS. We identify a novel sequence variant within a single IS patient that disrupts PTK7 function, consistent with a role for dysregulated Wnt activity in disease pathogenesis. Furthermore, we demonstrate that embryonic loss-of-gene function in maternal-zygotic ptk7 mutants (MZptk7) leads to vertebral anomalies associated with CS. Our data suggest novel molecular origins of, and genetic links between, congenital and idiopathic forms of disease. PMID:25182715

[Cutaneous hemangiomas and vascular malformations and associated pathology (Pascual-Castroviejo type II syndrome). Study of 41 patients].

PubMed

Pascual-Castroviejo, I; Pascual-Pascual, S I; Velázquez-Fragua, R; García, L; López-Gutiérrez, J C; Viaño-López, J; Martínez, V; Palencia, R

To describe the clinical, diagnostic and therapeutic features of this angiomatous neurocutaneous syndrome, which is the most frequent one, and to report a personal series of 41 patients. Forty one patients--31 females and 10 males--were studied during childhood and then, several patients were followed during many years, which allowed us to learn about the evolution of the abnormalities. The cutaneous lesions were classified as hemangiomas in 30 patients (73%) and as vascular malformations in 11 patients (27%). A cerebellar anomaly (unilateral hemispheric hypoplasia and Dandy-Walker malformation) was seen in 13 patients (31.5%) cerebral cortical dysplasia in 4 patients (10%), aortic arch coarctation in 6 patients (15%), and congenital cardiopathy in 5 patients (12%). The most frequent abnormalities were intracranial and/or extracranial vascular malformations. Persistence of the trigeminal artery was observed in 7 patients (17%), absence or severe hypoplasia of an internal carotid artery in 13 patients (32%), absence of a vertebral artery in 7 patients (17%), hypoplasia of intracranial arteries in 6 patients (15%) and aneurysmal enlargement of carotid or vertebral arteries in 5 patients (12%). Also were observed 4 patients (10%) with intracranial hemangioma, 2 (5%) with hemangioma in mediastinum, and 3 (7.5%) with intestinal hemangioma, all of which disappeared during the first years of life. Aneurysmal enlargement of the carotid and vertebral arteries and intracranial branches also disappeared after a process of progressive narrowing of the arterial lumen that caused complete obstruction of these arteries. At the same time the cutaneous hemangioma regressed. During this process, collateral vascularization through branches of the external carotid artery and of the non-affected branches of the contralateral intracranial arteries developed. This neurocutaneous syndrome is the most frequent one and it is associated with several types of vascular and non-vascular abnormalities which can involve any organ of the body. Internal and external hemangiomas and hemangiomatous lesions progress and tend to regress concomitantly.

A retrospective study of nineteen ataxic horses

PubMed Central

Nappert, Germain; Vrins, André; Breton, Luc; Beauregard, Michel

1989-01-01

A retrospective study of 19 ataxic horses admitted to the College of Veterinary Medicine of the University of Montreal during the period of January 1985 to December 1988 is presented. There were 11 cases of cervical vertebral malformation, four of equine degenerative myeloencephalopathy, two of equine protozoal myeloencephalitis, one each of vertebral osteomyelitis and intervertebral disc protrusion. The clinical diagnosis of ataxia in horses requires neurological, radiographic, myelographic, and laboratory examinations. ImagesFigure 1.Figure 2.Figure 3. PMID:17423438

"Serpentine-like syndrome"-A very rare multiple malformation syndrome characterised by brachioesophagus and vertebral anomalies.

PubMed

Beleza-Meireles, Ana; Steenhaut, Patricia; Hocq, Catheline; Clapuyt, Philippe; Bernard, Pierre; Debauche, Christian; Sznajer, Yves

2017-02-01

"Serpentine-like syndrome" is a severe and rare association of multiple congenital malformations, characterised by brachioesophagus, secondary intrathoracic stomach, and vertebral anomalies. Other associated anomalies have been described, such as malposition and herniation of abdominal organs. We report the natural history of a baby girl born at 29 weeks of gestation with intra uterine growth restriction, short neck, large rachischisis from cervical to thoracic spine, a very short oesophagus, thoracic stomach associated with a midline diaphragmatic hernia, malrotated gut and median cleft lip. Most of these anomalies were detected antenatally. Molecular karyotype was normal. She died at age 12 days. To our knowledge, the present patient represents the 8th report of a case of "Serpentine-like syndrome". Brachioesophagus and congenital vertebral anomalies, in particular rachischisis, are the cardinal features of this condition. All reported cases have been sporadic and the cause is still unknown. We believe that the specificity of the presentation as well as the similarities between available descriptions of patients suggests a common, yet to identify, molecular cause, possibly involving a developmental "toolkit"/homeobox gene or related pathways. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Single olfactory organ associated with prosencephalic malformation and cyclopia in a Xenopus laevis tadpole.

PubMed

Magrassi, L; Graziadei, P P

1987-06-02

A cyclops Xenopus laevis tadpole with a single olfactory organ is described. At a stage comparable to 48, the telencephalon was severely atrophic and only the region where the olfactory fibres terminated appeared to have the cytoarchitecture of the olfactory bulb. In this animal the central nervous system (CNS) appeared normally developed only posterior to the preoptic area. The hypothesis of a diencephalic origin of the region where the olfactory fibres terminated is discussed in the light of our previous results of olfactory placode transplantation. By analogy between this case and other malformations (cyclopia, holoprosencephaly) in higher vertebrates and humans, the need is emphasized for a more precise anatomical description of the olfactory input in related malformations.

Screening for bovine leukocyte adhesion deficiency, deficiency of uridine monophosphate synthase, complex vertebral malformation, bovine citrullinaemia, and factor XI deficiency in Holstein cows reared in Turkey.

PubMed

Meydan, Hasan; Yildiz, Mehmet A; Agerholm, Jørgen S

2010-10-07

Bovine leukocyte adhesion deficiency (BLAD), deficiency of uridine monophosphate synthase (DUMPS), complex vertebral malformation (CVM), bovine citrullinaemia (BC) and factor XI deficiency (FXID) are autosomal recessive hereditary disorders, which have had significant economic impact on dairy cattle breeding worldwide. In this study, 350 Holstein cows reared in Turkey were screened for BLAD, DUMPS, CVM, BC and FXID genotypes to obtain an indication on the importance of these defects in Turkish Holsteins. Genomic DNA was obtained from blood and the amplicons of BLAD, DUMPS, CVM, BC and FXID were obtained by using PCR. PCR products were digested with TaqI, AvaI and AvaII restriction enzymes for BLAD, DUMPS, and BC, respectively. These digested products and PCR product of FXID were analyzed by agarose gel electrophoresis stained with ethidium bromide. CVM genotypes were detected by DNA sequencing. Additionally, all genotypes were confirmed by DNA sequencing to determine whether there was a mutant allele or not. Fourteen BLAD, twelve CVM and four FXID carriers were found among the 350 Holstein cows examined, while carriers of DUMPS and BC were not detected. The mutant allele frequencies were calculated as 0.02, 0.017, and 0.006 for BLAD, CVM and FXID, respectively with corresponding carrier prevalence of 4.0% (BLAD), 3.4% (CVM) and 1.2% (FXID). This study demonstrates that carriers of BLAD, CVM and FXID are present in the Turkish Holstein population, although at a low frequency. The actual number of clinical cases is unknown, but sporadic cases may appear. As artificial insemination is widely used in dairy cattle breeding, carriers of BLAD, CVM and FXID are likely present within the population of breeding sires. It is recommended to screen breeding sires for these defective genes in order to avoid an unwanted spread within the population.

Screening for bovine leukocyte adhesion deficiency, deficiency of uridine monophosphate synthase, complex vertebral malformation, bovine citrullinaemia, and factor XI deficiency in Holstein cows reared in Turkey

PubMed Central

2010-01-01

Background Bovine leukocyte adhesion deficiency (BLAD), deficiency of uridine monophosphate synthase (DUMPS), complex vertebral malformation (CVM), bovine citrullinaemia (BC) and factor XI deficiency (FXID) are autosomal recessive hereditary disorders, which have had significant economic impact on dairy cattle breeding worldwide. In this study, 350 Holstein cows reared in Turkey were screened for BLAD, DUMPS, CVM, BC and FXID genotypes to obtain an indication on the importance of these defects in Turkish Holsteins. Methods Genomic DNA was obtained from blood and the amplicons of BLAD, DUMPS, CVM, BC and FXID were obtained by using PCR. PCR products were digested with TaqI, AvaI and AvaII restriction enzymes for BLAD, DUMPS, and BC, respectively. These digested products and PCR product of FXID were analyzed by agarose gel electrophoresis stained with ethidium bromide. CVM genotypes were detected by DNA sequencing. Additionally, all genotypes were confirmed by DNA sequencing to determine whether there was a mutant allele or not. Results Fourteen BLAD, twelve CVM and four FXID carriers were found among the 350 Holstein cows examined, while carriers of DUMPS and BC were not detected. The mutant allele frequencies were calculated as 0.02, 0.017, and 0.006 for BLAD, CVM and FXID, respectively with corresponding carrier prevalence of 4.0% (BLAD), 3.4% (CVM) and 1.2% (FXID). Conclusion This study demonstrates that carriers of BLAD, CVM and FXID are present in the Turkish Holstein population, although at a low frequency. The actual number of clinical cases is unknown, but sporadic cases may appear. As artificial insemination is widely used in dairy cattle breeding, carriers of BLAD, CVM and FXID are likely present within the population of breeding sires. It is recommended to screen breeding sires for these defective genes in order to avoid an unwanted spread within the population. PMID:20929557

Matrilin-1 expression is increased in the vertebral column of Atlantic salmon (Salmo salar L.) individuals displaying spinal fusions.

PubMed

Pedersen, Mona E; Takle, Harald; Ytteborg, Elisabeth; Veiseth-Kent, Eva; Enersen, Grethe; Færgestad, Ellen; Baeverfjord, Grete; Hannesson, Kirsten O

2011-12-01

We have previously characterized the development of vertebral fusions induced by elevated water temperature in Atlantic salmon. Molecular markers of bone and cartilage development together with histology were used to understand the complex pathology and mechanism in the development of this spinal malformation. In this study, we wanted to use proteomics, a non-hypothetical approach to screen for possible new markers involved in the fusion process. Proteins extracted from non-deformed and fused vertebrae of Atlantic salmon were therefore compared by two-dimensional electrophoresis (2DE) and MALDI-TOF analysis. Data analysis of protein spots in the 2DE gels demonstrated matrilin-1, also named cartilage matrix protein, to be the most highly up-regulated protein in fused compared with non-deformed vertebrae. Furthermore, real-time PCR analysis showed strong up-regulation of matrilin-1 mRNA in fused vertebrae. Immunohistochemistry demonstrated induced matrilin-1 expression in trans-differentiating cells undergoing a metaplastic shift toward chondrocytes in fusing vertebrae, whereas abundant expression was demonstrated in cartilaginous tissue and chordocytes of both non-deformed and fused vertebrae. These results identifies matrilin-1 as a new interesting candidate in the fusion process, and ratify the use of proteomic as a valuable technique to screen for markers involved in vertebral pathogenesis.

Leaping lopsided: a review of the current hypotheses regarding etiologies of limb malformations in frogs.

PubMed

Loeffler, I K; Stocum, D L; Fallon, J F; Meteyer, C U

2001-10-15

Recent progress in the investigation of limb malformations in free-living frogs has underlined the wide range in the types of limb malformations and the apparent spatiotemporal clustering of their occurrence. Here, we review the current understanding of normal and abnormal vertebrate limb development and regeneration and discuss some of the molecular events that may bring about limb malformation. Consideration of the differences between limb development and regeneration in amphibians has led us to the hypothesis that some of the observed limb malformations come about through misdirected regeneration. We report the results of a pilot study that supports this hypothesis. In this study, the distal aspect of the right hindlimb buds of X. laevis tadpoles was amputated at the pre-foot paddle stage. The tadpoles were raised in water from a pond in Minnesota at which 7% of surveyed newly metamorphosed feral frogs had malformations. Six percent (6 of 100) of the right limbs of the tadpoles raised in pond water developed abnormally. One truncated right limb was the only malformation in the control group, which was raised in dechlorinated municipal water. All unamputated limbs developed normally in both groups. Three major factors under consideration for effecting the limb malformations are discussed. These factors include environmental chemicals (primarily agrichemicals), encysted larvae (metacercariae) of trematode parasites, and increased levels of ultraviolet light. Emphasis is placed on the necessary intersection of environmental stressors and developmental events to bring about the specific malformations that are observed in free-living frog populations.

Leaping lopsided: a review of the current hypotheses regarding etiologies of limb malformations in frogs

USGS Publications Warehouse

Loeffler, I.K.; Stocum, D.L.; Fallon, J.F.; Meteyer, C.U.

2001-01-01

Recent progress in the investigation of limb malformations in free-living frogs has underlined the wide range in the types of limb malformations and the apparent spatiotemporal clustering of their occurrence. Here, we review the current understanding of normal and abnormal vertebrate limb development and regeneration and discuss some of the molecular events that may bring about limb malformation. Consideration of the differences between limb development and regeneration in amphibians has led us to the hypothesis that some of the observed limb malformations come about through misdirected regeneration. We report the results of a pilot study that supports this hypothesis. In this study, the distal aspect of the right hindlimb buds of X. laevis tadpoles was amputated at the pre-foot paddle stage. The tadpoles were raised in water from a pond in Minnesota at which 7% of surveyed newly metamorphosed feral frogs had malformations. Six percent (6 of 100) of the right limbs of the tadpoles raised in pond water developed abnormally. One truncated right limb was the only malformation in the control group, which was raised in dechlorinated municipal water. All unamputated limbs developed normally in both groups. Three major factors under consideration for effecting the limb malformations are discussed. These factors include environmental chemicals (primarily agrichemicals), encysted larvae (metacercariae) of trematode parasites, and increased levels of ultraviolet light. Emphasis is placed on the necessary intersection of environmental stressors and developmental events to bring about the specific malformations that are observed in free-living frog populations.

Neural Crest Origins of the Neck and Shoulder

PubMed Central

Matsuoka, Toshiyuki; Ahlberg, Per E.; Kessaris, Nicoletta; Iannarelli, Palma; Dennehy, Ulla; Richardson, William D.; McMahon, Andrew P.; Koentges, Georgy

2005-01-01

Summary The neck and shoulder region of vertebrates has undergone a complex evolutionary history. In order to identify its underlying mechanisms we map the destinations of embryonic neural crest and mesodermal stem cells using novel Cre-recombinase mediated transgenesis. The single-cell resolution of this genetic labelling reveals cryptic cell boundaries traversing seemingly homogeneous skeleton of neck and shoulders. Within this complex assembly of bones and muscles we discern a precise code of connectivity that mesenchymal stem cells of neural crest and mesodermal origin both obey as they form muscle scaffolds. Neural crest anchors the head onto the anterior lining of the shoulder girdle, while a Hox gene controlled mesoderm links trunk muscles to the posterior neck and shoulder skeleton. The skeleton that we identify as neural crest is specifically affected in human Klippel-Feil syndrome, Sprengel’s deformity and Arnold-Chiari I/II malformation, providing first insights into their likely aetiology. We identify genes involved in the cellular modularity of neck and shoulder skeleton and propose a new methodology for determining skeletal homologies that is based on muscle attachments. This has allowed us to trace the whereabouts of the cleithrum, the major shoulder bone of extinct land vertebrate ancestors which appears to survive as the scapular spine in living mammals. PMID:16034409

First approximation to congenital malformation rates in embryos and hatchlings of sea turtles.

PubMed

Bárcenas-Ibarra, Annelisse; de la Cueva, Horacio; Rojas-Lleonart, Isaias; Abreu-Grobois, F Alberto; Lozano-Guzmán, Rogelio Iván; Cuevas, Eduardo; García-Gasca, Alejandra

2015-03-01

Congenital malformations in sea turtles have been considered sporadical. Research carried out in the Mexican Pacific revealed high levels of congenital malformations in the olive ridley, but little or no information is available for other species. We present results from analyses of external congenital malformations in olive ridley, green, and hawskbill sea turtles from Mexican rookeries on the Pacific coast and Gulf of Mexico. We examined 150 green and hawksbill nests and 209 olive ridley nests during the 2010 and 2012 nesting seasons, respectively. Olive ridley eggs were transferred to a hatchery and incubated in styrofoam boxes. Nests from the other two species were left in situ. Number of eggs, live and dead hatchlings, and eggs with or without embryonic development were registered. Malformation frequency was evaluated with indices of prevalence and severity. Mortality levels, prevalence and severity were higher in olive ridley than in hawksbill and green sea turtles. Sixty-three types of congenital malformations were observed in embryos, and dead or live hatchlings. Of these, 38 are new reports; 35 for wild sea turtles, three for vertebrates. Thirty-one types were found in hawksbill, 23 in green, and 59 in olive ridley. The head region showed a higher number of malformation types. Malformation levels in the olive ridley were higher than previously reported. Olive ridleys seem more prone to the occurrence of congenital malformations than the other two species. Whether the observed malformation levels are normal or represent a health problem cannot be currently ascertained without long-term assessments. © 2015 Wiley Periodicals, Inc.

Analysis of Maternal Risk Factors Associated With Congenital Vertebral Malformations

PubMed Central

Hesemann, Jennifer; Lauer, Emily; Ziska, Stephen; Noonan, Kenneth; Nemeth, Blaise; Scott-Schwoerer, Jessica; McCarty, Catherine; Rasmussen, Kristen; Goldberg, Jacob M.; Sund, Sarah; Eickhoff, Jens; Raggio, Cathleen L.; Giampietro, Philip F.

2014-01-01

Study Design A retrospective chart review of cases with congenital vertebral malformations (CVM) and controls with normal spine morphology. Objective To determine the relative contribution of maternal environmental factors (MEF) during pregnancy including maternal insulin dependent diabetes mellitus, valproic acid, alcohol, smoking, hyperthermia, twin gestation, assisted reproductive technology, in-vitro fertilization and maternal clomiphene usage to CVM development. Summary of Background Data Congenital vertebral malformations (CVM) represent defects in formation and segmentation of somites occurring with an estimated incidence of between 0.13–0.50 per 1000 live births. CVM may be associated with congenital scoliosis, Klippel-Feil syndrome, hemifacial microsomia and VACTERL syndromes, and represent significant morbidity due to pain and cosmetic disfigurement. Methods A multicenter retrospective chart review of 229 cases with CVM and 267 controls with normal spine morphology between the ages of 1–50 years was performed in order to obtain the odds ratio (OR) of MEF related to CVM among cases vs. controls. CVM due to an underlying syndrome associated with a known gene mutation or chromosome etiology were excluded. An imputation based analysis was performed in which subjects with no documentation of MEF history were treated as no maternal exposure.” Univariate and multivariate analysis was conducted to calculate the OR. Results Of the 229 total cases, 104 cases had single or multiple CVM without additional congenital malformations (CM) (Group 1) and 125 cases had single or multiple CVM and additional CM (Group 2). Nineteen percent of total cases had an identified MEF. The OR (95% CI, P-value) for MEF history for Group 1 was 6.0 (2.4–15.1, P<0.001) in the univariate analysis. The OR for MEF history in Group 2 was 9.1 (95%CI, P-value) (3.8–21.6, P<0.001) in the univariate analysis. The results were confirmed in the multivariate analysis, after adjusting for age, gender, and institution. Discussion These results support a hypothesis for an association between the above MEF during pregnancy and CVM and have implications for development of prevention strategies. Further prospective studies are needed to quantify association between CVM and specific MEF. PMID:23446706

Incorporating Amphibian Malformations into Inquiry-Based Learning

ERIC Educational Resources Information Center

Talley, Brooke L.

2007-01-01

Amphibians, a class of vertebrates consisting of frogs and toads, salamanders, and caecilians, are excellent organisms for middle school science students to study because of their ecological significance. Because they exchange oxygen and carbon dioxide through their skin, amphibians absorb any chemicals or substances present in their immediate…

Simulating transitional hydrodynamics of the cerebrospinal fluid at extreme scale

NASA Astrophysics Data System (ADS)

Jain, Kartik; Roller, Sabine; Mardal, Kent-Andre

Chiari malformation type I is a disorder characterized by the herniation of cerebellar tonsils into the spinal canal through the foramen magnum resulting in obstruction to cerebrospinal fluid (CSF) outflow. The flow of pulsating bidirectional CSF is of acutely complex nature due to the anatomy of the conduit containing it - the subarachnoid space. We report lattice Boltzmann method based direct numerical simulations on patient specific cases with spatial resolution of 24 μm amounting meshes of up to 2 billion cells conducted on 50000 cores of the Hazelhen supercomputer in Stuttgart. The goal is to characterize intricate dynamics of the CSF at resolutions that are of the order of Kolmogorov microscales. Results unfold velocity fluctuations up to ~ 10 KHz , turbulent kinetic energy ~ 2 times of the mean flow energy in Chiari patients whereas the flow remains laminar in a control subject. The fluctuations confine near the cranio-vertebral junction and are commensurate with the extremeness of pathology and the extent of herniation. The results advocate that the manifestation of pathological conditions like Chiari malformation may lead to transitional hydrodynamics of the CSF, and a prudent calibration of numerical approach is necessary to avoid overlook of such phenomena.

TBX15 mutations cause craniofacial dysmorphism, hypoplasia of scapula and pelvis, and short stature in Cousin syndrome.

PubMed

Lausch, Ekkehart; Hermanns, Pia; Farin, Henner F; Alanay, Yasemin; Unger, Sheila; Nikkel, Sarah; Steinwender, Christoph; Scherer, Gerd; Spranger, Jürgen; Zabel, Bernhard; Kispert, Andreas; Superti-Furga, Andrea

2008-11-01

Members of the evolutionarily conserved T-box family of transcription factors are important players in developmental processes that include mesoderm formation and patterning and organogenesis both in vertebrates and invertebrates. The importance of T-box genes for human development is illustrated by the association between mutations in several of the 17 human family members and congenital errors of morphogenesis that include cardiac, craniofacial, and limb malformations. We identified two unrelated individuals with a complex cranial, cervical, auricular, and skeletal malformation syndrome with scapular and pelvic hypoplasia (Cousin syndrome) that recapitulates the dysmorphic phenotype seen in the Tbx15-deficient mice, droopy ear. Both affected individuals were homozygous for genomic TBX15 mutations that resulted in truncation of the protein and addition of a stretch of missense amino acids. Although the mutant proteins had an intact T-box and were able to bind to their target DNA sequence in vitro, the missense amino acid sequence directed them to early degradation, and cellular levels were markedly reduced. We conclude that Cousin syndrome is caused by TBX15 insufficiency and is thus the human counterpart of the droopy ear mouse.

The presentation and management of complex female genital malformations.

PubMed

Acién, Pedro; Acién, Maribel

2016-01-01

Common uterine anomalies are important owing to their impact on fertility, and complex mesonephric anomalies and certain Müllerian malformations are particularly important because they cause serious clinical symptoms and affect woman's quality of life, in addition to creating fertility problems. In these cases of complex female genital tract malformations, a correct diagnosis is essential to avoid inappropriate and/or unnecessary surgery. Therefore, acquiring and applying the appropriate embryological knowledge, management and therapy is a challenge for gynaecologists. Here, we considered complex malformations to be obstructive anomalies and/or those associated with cloacal and urogenital sinus anomalies, urinary and/or extragenital anomalies, or other clinical implications or symptoms creating a difficult differential diagnosis. A diligent and comprehensive search of PubMed and Scopus was performed for all studies published from 1 January 2011 to 15 April 2015 (then updated up to September 2015) using the following search terms: 'management' in combination with either 'female genital malformations' or 'female genital tract anomalies' or 'Müllerian anomalies'. The MeSH terms 'renal agenesis', 'hydrocolpos', 'obstructed hemivagina' 'cervicovaginal agenesis or atresia', 'vaginal agenesis or atresia', 'Herlyn-Werner-Wunderlich syndrome', 'uterine duplication' and 'cloacal anomalies' were also used to compile a list of all publications containing these terms since 2011. The basic embryological considerations for understanding female genitourinary malformations were also revealed. Based on our experience and the updated literature review, we studied the definition and classification of the complex malformations, and we analysed the clinical presentation and different therapeutic strategies for each anomaly, including the embryological and clinical classification of female genitourinary malformations. From 755 search retrieved references, 230 articles were analysed and 120 studied in detail. They were added to those included in a previous systematic review. Here, we report the clinical presentation and management of: agenesis or hypoplasia of one urogenital ridge; unilateral renal agenesis and ipsilateral blind or obstructed hemivagina or unilateral cervicovaginal agenesis; cavitated and non-communicating uterine horns and Müllerian atresias or agenesis, including Rokitansky syndrome; anomalies of the cloaca and urogenital sinus, including congenital vagino-vesical fistulas and cloacal anomalies; malformative combinations and other complex malformations. The clinical symptoms and therapeutic strategies for each complex genitourinary malformation are discussed. In general, surgical techniques to correct genital malformations depend on the type of anomaly, its complexity, the patient's symptoms and the correct embryological interpretation of the anomaly. Most anomalies can typically be resolved vaginally or by hysteroscopy, but laparoscopy or laparotomy is often required as well. We also include additional discussion of the catalogue and classification systems for female genital malformations, the systematic association between renal agenesis and ipsilateral genital malformation, and accessory and cavitated uterine masses. Knowledge of the correct genitourinary embryology is essential for the understanding, study, diagnosis and subsequent treatment of genital malformations, especially complex ones and those that lead to gynaecological and reproductive problems, particularly in young patients. Some anomalies may require complex surgery involving multiple specialties, and patients should therefore be referred to centres that have experience in treating complex genital malformations. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Developmental mechanisms of intervertebral disc and vertebral column formation.

PubMed

Lawson, Lisa Y; Harfe, Brian D

2017-11-01

The vertebral column consists of repeating units of ossified vertebrae that are adjoined by fibrocartilagenous intervertebral discs. These structures form from the embryonic notochord and somitic mesoderm. In humans, congenital malformations of the vertebral column include scoliosis, kyphosis, spina bifida, and Klippel Feil syndrome. In adulthood, a common malady affecting the vertebral column includes disc degeneration and associated back pain. Indeed, recent reports estimate that low back pain is the number one cause of disability worldwide. Our review provides an overview of the molecular mechanisms underlying vertebral column morphogenesis and intervertebral disc development and maintenance, with an emphasis on what has been gleaned from recent genetic studies in mice. The aim of this review is to provide a developmental framework through which vertebral column formation can be understood so that ultimately, research scientists and clinicians alike can restore disc health with appropriately designed gene and cell-based therapies. WIREs Dev Biol 2017, 6:e283. doi: 10.1002/wdev.283 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

A primary phosphorus-deficient skeletal phenotype in juvenile Atlantic salmon Salmo salar: the uncoupling of bone formation and mineralization.

PubMed

Witten, P E; Owen, M A G; Fontanillas, R; Soenens, M; McGurk, C; Obach, A

2016-02-01

To understand the effect of low dietary phosphorus (P) intake on the vertebral column of Atlantic salmon Salmo salar, a primary P deficiency was induced in post-smolts. The dietary P provision was reduced by 50% for a period of 10 weeks under controlled conditions. The animal's skeleton was subsequently analysed by radiology, histological examination, histochemical detection of minerals in bones and scales and chemical mineral analysis. This is the first account of how a primary P deficiency affects the skeleton in S. salar at the cellular and at the micro-anatomical level. Animals that received the P-deficient diet displayed known signs of P deficiency including reduced growth and soft, pliable opercula. Bone and scale mineral content decreased by c. 50%. On radiographs, vertebral bodies appear small, undersized and with enlarged intervertebral spaces. Contrary to the X-ray-based diagnosis, the histological examination revealed that vertebral bodies had a regular size and regular internal bone structures; intervertebral spaces were not enlarged. Bone matrix formation was continuous and uninterrupted, albeit without traces of mineralization. Likewise, scale growth continues with regular annuli formation, but new scale matrix remains without minerals. The 10 week long experiment generated a homogeneous osteomalacia of vertebral bodies without apparent induction of skeletal malformations. The experiment shows that bone formation and bone mineralization are, to a large degree, independent processes in the fish examined. Therefore, a deficit in mineralization must not be the only cause of the alterations of the vertebral bone structure observed in farmed S. salar. It is discussed how the observed uncoupling of bone formation and mineralization helps to better diagnose, understand and prevent P deficiency-related malformations in farmed S. salar. © 2015 The Authors.Journal of Fish Biology published by John Wiley & Sons Ltd on behalf of The Fisheries Society of the British Isles.

The Amniote Oculomotor Complex.

PubMed

Company, Verónica; Moreno-Bravo, Juan Antonio; Perez-Balaguer, Ariadna; Puelles, Eduardo

2018-04-16

The oculomotor (OM) complex is a combination of somatic and parasympatethic neurons. The correct development and wiring of this cranial pair is essential to perform basic functions: eyeball and eyelid movements, pupillary constriction, and lens accommodation. The improper formation or function of this nucleus leads pathologies such as strabismus. We describe the OM organization and function in different vertebrate brains, including chick, mouse, and human. The morphological localization is detailed, as well as the spatial relation with the trochlear nucleus in order to adjust some misleading anatomical topographic descriptions. We detailed the signaling processes needed for the specification of the OM neurons. The transcriptional programs driven the specification and differentiation of these neurons are partially determined. We summarized recent genetic studies that have led to the identification of guidance mechanisms involved in the migration, axon pathfinding, and targeting of the OM neurons. Finally, we overviewed the pathology associated to genetic malformations in the OM development and related clinical alterations. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Fetus with Casamassima-Morton-Nance Syndrome and Limb-Body Wall Defect: Presentation of a Novel Association and Review of the Phenotype.

PubMed

Salinas-Torres, Victor M

2016-01-01

In 1981, Casamassima and colleagues described an autosomal recessive syndrome of spondylocostal dysostosis associated with anal and urogenital anomalies. Here, I describe 1 new fetus who presented with limb-body wall defect as a novel association, compile 7 patients, and review the clinical phenotype of Casamassima-Morton-Nance syndrome. This appears to be the 1st Casamassima-Morton-Nance syndrome fetus with this complex malformation. In light of this manifestation, a detailed comparative phenotypic analysis of published patients revealed a heterogeneous syndrome with significant clinical variability. Accordingly, it is proposed that Casamassima-Morton-Nance syndrome should be considered in those patients with the combination of a short and asymmetric thorax with rib and vertebral anomalies and scoliosis (spondylocostal-like pattern), anal atresia, absent external genitalia, renal and urethral abnormalities (caudal dysgenesis complex), craniofacial dysmorphic features (mainly flat nose with anteverted nares, low-set/abnormal ears, and short neck), hydrops, oligohydramnios, and a poor clinical outcome.

Gorlin-Goltz syndrome and neoplasms: a case study.

PubMed

Lopes, Nilza N F; Caran, Eliana M; Lee, Maria Lucia; Silva, Nasjla Saba; Rocha, André Caroli; Macedo, Carla R D

2010-01-01

Gorlin syndrome is a rare autosomal dominant disorder exhibiting high penetrance and variable expressivity. It is characterized by facial dysmorphism, skeletal anomalies, multiple basal cell carcinomas, odontogenic keratocysts (OKC), palmar and plantar pits, bifid ribs, vertebral anomalies and a variety of other malformations. Various neoplasms, such as medulloblastomas, meningiomas, ovarian and cardiac fibromas are also found in this syndrome. To describe a twelve-year-old patient with Gorlin-Goltz syndrome, with basal cell carcinomas and promyelocytic leukemia developed after receiving craniospinal radiation for a medulloblastoma. Bifid ribs as well as mandibular and maxillar OKC were also diagnosed Conclusion: The patient with Gorlin-Goltz syndrome should receive close follow-up for early detection of malformations nd malignant neoplasias.

Cystic angiomatosis of the craniocervical junction associated with Chiari I malformation: case report and review of the literature.

PubMed

Pavanello, Marco; Piatelli, Gianluca; Ravegnani, Marcello; Consales, Alessandro; Rossi, Andrea; Nozza, Paolo; Milanaccio, Claudia; Carbone, Marco; Cama, Armando

2007-06-01

Cystic angiomatosis of the skull and spine is an exceptionally rare, benign vascular lesion. Both the vertebral bones and the skull may be affected. Diagnosis and treatment of this disease is multidisciplinary. Histological examination is ultimately required to make a diagnosis. When the craniocervical junction is involved, the site of biopsy should be carefully selected so as to reduce procedure-related morbidity, including cerebrospinal fluid leakage and spinal deformity. We present a case report of a 4-year-old boy with cystic angiomatosis of the skull base and upper cervical spine associated with a Chiari I malformation and provide a review of the pertinent literature.

An endovascular option is the final treatment for a giant arteriovenous malformation.

PubMed

Benedetto, Filippo; Pipitò, Narayana; Barillà, David; Spinelli, Domenico; Stilo, Francesco; Spinelli, Francesco

2014-11-01

We report the case of a 58-year-old man presented with bleeding ulcer of the left arm caused by a high-flow type-C arteriovenous malformation (AVM), feed by branches from both the subclavian arteries. He had been previously treated with AVM sclerotherapy, embolization, humeral artery endografting, and open surgery. We urgently performed coil embolization of the left vertebral artery, and we covered the huge subclavian artery by a thoracic endograft. Then, we embolized the right tyrocervical trunk. The result was an immediate interruption of bleeding. At 12 months, the patient had no neurologic complications, and the upper limb continued to decompress. Copyright © 2014 Elsevier Inc. All rights reserved.

Genetic basis of human left-right asymmetry disorders.

PubMed

Deng, Hao; Xia, Hong; Deng, Sheng

2015-01-27

Humans and other vertebrates exhibit left-right (LR) asymmetric arrangement of the internal organs, and failure to establish normal LR asymmetry leads to internal laterality disorders, including situs inversus and heterotaxy. Situs inversus is complete mirror-imaged arrangement of the internal organs along LR axis, whereas heterotaxy is abnormal arrangement of the internal thoraco-abdominal organs across LR axis of the body, most of which are associated with complex cardiovascular malformations. Both disorders are genetically heterogeneous with reduced penetrance, presumably because of monogenic, polygenic or multifactorial causes. Research in genetics of LR asymmetry disorders has been extremely prolific over the past 17 years, and a series of loci and disease genes involved in situs inversus and heterotaxy have been described. The review highlights the classification, chromosomal abnormalities, pathogenic genes and the possible mechanism of human LR asymmetry disorders.

Antenatal hemorrhage of a cervical lymphatic malformation presenting as a draining neck mass: An unusual presentation.

PubMed

Haricharan, R N; Nawaz, M; Bettolli, M; Ferretti, E

2014-01-01

Lymphatic malformations in the neck can present as large fetal neck masses causing airway obstructions with potential perinatal demise and can pose a therapeutic challenge. We present a rare case of prenatally diagnosed large fetal neck mass with features of lymphatic malformation with intralesional hemorrhage of uncertain origin. Postnatal evaluation showed a complex cystic-solid lesion eroding through the skin with an open wound that made it clinically hard to differentiate from a teratoma. Given that malignancy could not be completely ruled out, surgery was favored. Final pathology showed a complex lymphatic malformation with intralesional hemorrhage, despite having no associated capillary, venous or arterial malformations.

‘Monster… -omics’: on segmentation, re-segmentation, and vertebrae formation in amphibians and other vertebrates

PubMed Central

2013-01-01

Background The axial skeleton is one of the defining evolutionary landmarks of vertebrates. How this structure develops and how it has evolved in the different vertebrate lineages is, however, a matter of debate. Vertebrae and vertebral structures are derived from the embryonic somites, although the mechanisms of development are different between lineages. Discussion Using the anecdotal description of a teratological newt (Triturus dobrogicus) with an unusual malformation in its axial skeleton, we review, compare, and discuss the development of vertebral structures and, in particular, the development of centra from somitic cellular domains in different vertebrate groups. Vertebrae development through re-segmentation of the somitic sclerotomal cells is considered the general mechanism among vertebrates, which has been generalized from studies in amniotic model organisms. The prevalence of this mechanism among anamniotes is, however, controversial. We propose alternative developmental mechanisms for vertebrae formation that should be experimentally tested. Summary Research in model organisms, especially amniotes, is laying the foundations for a thorough understanding of the mechanisms of development of the axial skeleton in vertebrates, foundations that should expand the extent of future comparative studies. Although immersed in the ‘-omics’ era, we emphasize the need for an integrative and organismal approach in evolutionary developmental biology for a better understanding of the causal role of development in the evolution of morphological diversity in nature. PMID:23577917

Targeted Resequencing of 29 Candidate Genes and Mouse Expression Studies Implicate ZIC3 and FOXF1 in Human VATER/VACTERL Association.

PubMed

Hilger, Alina C; Halbritter, Jan; Pennimpede, Tracie; van der Ven, Amelie; Sarma, Georgia; Braun, Daniela A; Porath, Jonathan D; Kohl, Stefan; Hwang, Daw-Yang; Dworschak, Gabriel C; Hermann, Bernhard G; Pavlova, Anna; El-Maarri, Osman; Nöthen, Markus M; Ludwig, Michael; Reutter, Heiko; Hildebrandt, Friedhelm

2015-12-01

The VATER/VACTERL association describes the combination of congenital anomalies including vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects. As mutations in ciliary genes were observed in diseases related to VATER/VACTERL, we performed targeted resequencing of 25 ciliary candidate genes as well as disease-associated genes (FOXF1, HOXD13, PTEN, ZIC3) in 123 patients with VATER/VACTERL or VATER/VACTERL-like phenotype. We detected no biallelic mutation in any of the 25 ciliary candidate genes; however, identified an identical, probably disease-causing ZIC3 missense mutation (p.Gly17Cys) in four patients and a FOXF1 de novo mutation (p.Gly220Cys) in a further patient. In situ hybridization analyses in mouse embryos between E9.5 and E14.5 revealed Zic3 expression in limb and prevertebral structures, and Foxf1 expression in esophageal, tracheal, vertebral, anal, and genital tubercle tissues, hence VATER/VACTERL organ systems. These data provide strong evidence that mutations in ZIC3 or FOXF1 contribute to VATER/VACTERL. © 2015 WILEY PERIODICALS, INC.

Disruption of long-distance highly conserved noncoding elements in neurocristopathies.

PubMed

Amiel, Jeanne; Benko, Sabina; Gordon, Christopher T; Lyonnet, Stanislas

2010-12-01

One of the key discoveries of vertebrate genome sequencing projects has been the identification of highly conserved noncoding elements (CNEs). Some characteristics of CNEs include their high frequency in mammalian genomes, their potential regulatory role in gene expression, and their enrichment in gene deserts nearby master developmental genes. The abnormal development of neural crest cells (NCCs) leads to a broad spectrum of congenital malformation(s), termed neurocristopathies, and/or tumor predisposition. Here we review recent findings that disruptions of CNEs, within or at long distance from the coding sequences of key genes involved in NCC development, result in neurocristopathies via the alteration of tissue- or stage-specific long-distance regulation of gene expression. While most studies on human genetic disorders have focused on protein-coding sequences, these examples suggest that investigation of genomic alterations of CNEs will provide a broader understanding of the molecular etiology of both rare and common human congenital malformations. © 2010 New York Academy of Sciences.

Ontogeny of the vertebral column of Eleutherodactylus johnstonei (Anura: Eleutherodactylidae) reveals heterochronies relative to metamorphic frogs.

PubMed

Meza-Joya, Fabio Leonardo; Ramos-Pallares, Eliana Patricia; Ramírez-Pinilla, Martha Patricia

2013-07-01

Over the last century, the morphogenesis of the vertebral column has been considered as a highly conserved process among anurans. This statement is based on the study of few metamorphic taxa, ignoring the role of developmental mechanisms underlying the evolution of specialized life-histories. Direct development in anurans has been regarded as evolutionarily derived and involves developmental recapitulation and repatterning at different levels in all amphibian taxa studied so far. Herein, we analyze the vertebral column morphogenesis of the direct-developing frog Eleutherodactylus johnstonei, describing the sequence of chondrification and ossification, based on cleared and double-stained specimens from early stage embryos to adults. In general, our results show that the morphogenesis of the vertebral column in E. johnstonei recapitulates the ancestral tadpole-like pattern of development. However, the analysis of the sequence of events using heterochrony plots shows important heterocronies relative to metamorphic species, such as a delay in the chondrification of the vertebral centra and in osteogenesis. These ontogenetic peculiarities may represent derived traits in direct-developing frogs and are possibly correlated with its unusual life history. In addition, several features of the vertebral column of E. johnstonei are highly variable from its typical morphology. We report some malformations and small deviations, which do not seem to affect the survival of individuals. These anomalies have also been found in other frogs, and include many vertebral defects, such as vertebral fusion, and vertebral preclusion and/or induction. Copyright © 2013 Wiley Periodicals, Inc.

Esophageal atresia in newborns: a wide spectrum from the isolated forms to a full VACTERL phenotype?

PubMed

La Placa, Simona; Giuffrè, Mario; Gangemi, Antonella; Di Noto, Stefania; Matina, Federico; Nociforo, Federica; Antona, Vincenzo; Di Pace, Maria Rita; Piccione, Maria; Corsello, Giovanni

2013-07-10

VATER association was first described in 1972 by Quan and Smith as an acronym which identifies a non-random co-occurrence of Vertebral anomalies, Anal atresia, Tracheoesophageal fistula and/or Esophageal atresia, Radial dysplasia. It is even possible to find out Cardiovascular, Renal and Limb anomalies and the acronym VACTERL was adopted, also, embodying Vascular, as single umbilical artery, and external genitalia anomalies. Data on patients with esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) admitted in the Neonatal Intensive Care Unit (NICU) between January 2003 and January 2013 were evaluated for the contingent occurrence of typical VACTERL anomalies (VACTERL-type) and non tipical VACTERL anomalies (non-VACTERL-type). The inclusion criterion was the presence of EA with or without TEF plus two or more of the following additional malformations: vertebral defects, anal atresia, cardiovascular defects, renal anomalies and lower limb deformities, like radial dysplasia. Among 52 patients with EA/TEF, 20 (38,4%) had isolated EA and 7 (21,8%) had a recognized etiology such a syndrome and therefore were excluded. Among 32 infants with EA and associated malformations, 15 (46,8%) had VACTERL association. The most common anomalies were congenital heart defects (73,3%), followed by vertebral anomalies (66,6%). Many patients also had additional non-VACTERL-type defects. Single umbilical artery was the most common one followed by nervous system abnormalities and anomalies of toes. Between the groups of infants with VACTERL type and non-VACTERL-type anomalies, there are several overlapping data regarding both the tipically described spectrum and the most frequently reported non-VACTERL-type malformations. Thus, it is possible to differentiate infants with a full phenotype (VACTERL full phenotype) and patients that do not meet all the criteria mentioned above, but with some homologies with the first group (VACTERL partial phenotype). The high frequency of non-VACTERL-type anomalies encountered in full and partial phenotype patients would suggest the need for an extension of the clinical criteria for the diagnosis of VACTERL association and also for pre- and post-operative management and follow-up in the short and long term.

Increased Prevalence of Cerebrovascular Disease in Hospitalized Patients with Ehlers-Danlos Syndrome.

PubMed

Kim, Sarasa T; Cloft, Harry; Flemming, Kelly D; Kallmes, David F; Lanzino, Giuseppe; Brinjikji, Waleed

2017-08-01

Small studies have suggested that Ehlers-Danlos syndrome (EDS) is associated with a number of cerebrovascular complications. We sought to determine whether a clinical diagnosis of EDS is associated with a higher prevalence of cerebrovascular diseases than the general population by performing a case-control study of hospitalized patients in the Nationwide Inpatient Sample (NIS). Using the 2000-2012 NIS, we performed a case-control study matching cases of EDS to controls without such a diagnosis. The prevalence of various cerebrovascular diseases between the 2 groups was compared, and multivariate logistic regression was used to adjust for suspected comorbidities. Between 2000 and 2012, there were a total of 9067 discharges carrying a diagnosis of EDS. On univariate analysis, patients with EDS were more likely to be hospitalized for carotid dissection (.2% versus .01%, odds ratio [OR] = 18.0, confidence interval [CI] = 2.41-135.12, P < .0001), vertebral dissection (.1% versus 0%, P = .008), cervical artery aneurysm (.1% versus .01%, OR = 9.01, CI = 1.14-71.11, P < .0001), cerebral aneurysm (.4% versus .09%, OR = 4.89, CI = 2.28-10.47, P < .0001), and cerebrovascular malformation (.1% versus .02%, OR = 5, CI = 1.10-22.85, P = .021), compared to the controls. On multivariate analysis adjusted for age, race, and comorbidities, EDS patients had significantly higher odds of carotid dissection (OR = 15.02, CI = 3.08-270.87, P < .0001), vertebral dissection (OR = 2406539.5, P = .0037), cervical artery aneurysm (OR = 11.75, CI = 2.11-220.71, P = .0026), cerebral aneurysm (OR = 5.59, CI = 2.69-13.18, P < .0001), and cerebrovascular malformation (OR = 4.67, CI = 1.20-30.87, P = .0243). Carotid and vertebral dissections, cervical and cerebral aneurysms, as well as other cerebrovascular malformations are more common in hospitalized patients with EDS compared to controls. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

A Review of Selected Genes with Known Effects on Performance and Health of Cattle

PubMed Central

Casas, Eduardo; Kehrli, Marcus E.

2016-01-01

There are genetic conditions that influence production in dairy and beef cattle. The objective of this review was to describe relevant genetic conditions that have been associated with productivity and health in cattle. Genes or genomic regions that have been identified as a candidate for the condition will be included, and the genetic basis of the condition will be defined. Genes and genetic conditions included in this review are bovine leukocyte adhesion deficiency, deficiency of the uridine monophosphate synthase, bovine chronic interstitial nephritis, horn development, myostatin, complex vertebral malformation, leptin, osteopetrosis, apoptosis peptide activating factor 1, chondrodysplastic dwarfism, caseins, calpastatin, umbilical hernia, lactoglobulin, citrullinemia, cholesterol deficiency, prions, thyroglobulin, diacylglycerol acyltransferase, syndactyly, maple syrup urine disease, slick hair, Factor XI deficiency, and μ-Calpain. This review is not meant to be comprehensive, and relevant information is provided to ascertain genetic markers associated with the conditions. PMID:28018909

Anaesthetic management of a child with massive extracranial arteriovenous malformation

PubMed Central

Shamim, Faisal; Ullah, Hameed; Rehman, Azhar

2012-01-01

Vascular tumors affect the head and neck commonly but arteriovenous malformations are rare. Vascular malformations are often present at birth and grow with the patient, usually only becoming significant later in childhood. Embolization has been the mainstay of treatment in massive and complex arteriovenous malformations. We present a case of massive extracranial arteriovenous malformation in a 7-year-old boy causing significant workload on right heart and respiratory distress. The management of angioembolization under general anaesthesia and anaesthetic concerns are presented. PMID:22345959

Interstitial 1q21.1 Microdeletion Is Associated with Severe Skeletal Anomalies, Dysmorphic Face and Moderate Intellectual Disability.

PubMed

Gamba, Bruno F; Zechi-Ceide, Roseli M; Kokitsu-Nakata, Nancy M; Vendramini-Pittoli, Siulan; Rosenberg, Carla; Krepischi Santos, Ana C V; Ribeiro-Bicudo, Lucilene; Richieri-Costa, Antonio

2016-11-01

We report on a Brazilian patient with a 1.7-Mb interstitial microdeletion in chromosome 1q21.1. The phenotypic characteristics include microcephaly, a peculiar facial gestalt, cleft lip/palate, and multiple skeletal anomalies represented by malformed phalanges, scoliosis, abnormal modeling of vertebral bodies, hip dislocation, abnormal acetabula, feet anomalies, and delayed neuropsychological development. Deletions reported in this region are clinically heterogeneous, ranging from subtle phenotypic manifestations to severe congenital heart defects and/or neurodevelopmental findings. A few genes within the deleted region are associated with congenital anomalies, mainly the RBM8A , DUF1220 , and HYDIN2 paralogs. Our patient presents with a spectrum of unusual malformations of 1q21.1 deletion syndrome not reported up to date.

Interstitial 1q21.1 Microdeletion Is Associated with Severe Skeletal Anomalies, Dysmorphic Face and Moderate Intellectual Disability

PubMed Central

Gamba, Bruno F.; Zechi-Ceide, Roseli M.; Kokitsu-Nakata, Nancy M.; Vendramini-Pittoli, Siulan; Rosenberg, Carla; Krepischi Santos, Ana C.V.; Ribeiro-Bicudo, Lucilene; Richieri-Costa, Antonio

2016-01-01

We report on a Brazilian patient with a 1.7-Mb interstitial microdeletion in chromosome 1q21.1. The phenotypic characteristics include microcephaly, a peculiar facial gestalt, cleft lip/palate, and multiple skeletal anomalies represented by malformed phalanges, scoliosis, abnormal modeling of vertebral bodies, hip dislocation, abnormal acetabula, feet anomalies, and delayed neuropsychological development. Deletions reported in this region are clinically heterogeneous, ranging from subtle phenotypic manifestations to severe congenital heart defects and/or neurodevelopmental findings. A few genes within the deleted region are associated with congenital anomalies, mainly the RBM8A, DUF1220, and HYDIN2 paralogs. Our patient presents with a spectrum of unusual malformations of 1q21.1 deletion syndrome not reported up to date. PMID:27920638

Diprosopia revisited in light of the recognized role of neural crest cells in facial development.

PubMed

Carles, D; Weichhold, W; Alberti, E M; Léger, F; Pigeau, F; Horovitz, J

1995-01-01

The aim of this study is to compare the theory of embryogenesis of the face with human diprosopia. This peculiar form of conjoined twinning is of great interest because 1) only the facial structures are duplicated and 2) almost all cases have a rather monomorphic pattern. The hypothesis is that an initial duplication of the notochord leads to two neural plates and subsequently duplicated neural crests. In those conditions, derivatives of the neural crests will be partially or totally duplicated; therefore, in diprosopia, the duplicated facial structures would be considered to be neural crest derivatives. If these structures are identical to those that are experimentally demonstrated to be neural crest derivatives in animals, these findings are an argument to apply this theory of facial embryogenesis in man. Serial horizontal sections of the face of two diprosopic fetuses (11 and 21 weeks gestation) were studied macro- and microscopically to determine the external and internal structures that are duplicated. Complete postmortem examination was performed in search for additional malformations. The face of both fetuses showed a very similar morphologic pattern with duplication of ocular, nasal, and buccal structures. The nasal fossae and the anterior part of the tongue were also duplicated, albeit the posterior part and the pharyngolaryngeal structures were unique. Additional facial clefts were present in both fetuses. Extrafacial anomalies were represented by a craniorachischisis, two fused vertebral columns and, in the older fetus, by a complex cardiac malformation morphologically identical to malformations induced by removal or grafting of additional cardiac neural crest cells in animals. These pathological findings could identify the facial structures that are neural crest derivatives in man. They are similar to those experimentally demonstrated to be neural crest derivatives in animals. In this respect, diprosopia could be considered as the end of a spectrum, whereas the other end is agnathia-holoprosencephaly complex. This assumption has to be discussed, but we want to draw attention to the fact that diprosopia must not be considered as a curious form of conjoined twinning, but as a major means of bringing us a better knowledge of the facial embryogenesis in man.

Pulmonary hypertensive crisis following ethanol sclerotherapy for a complex vascular malformation.

PubMed

Cordero-Schmidt, G; Wallenstein, M B; Ozen, M; Shah, N A; Jackson, E; Hovsepian, D M; Palma, J P

2014-09-01

Anhydrous ethanol is a commonly used sclerotic agent for treating vascular malformations. We describe the case of a full-term 15-day-old female with a complex venolymphatic malformation involving the face and orbit. During treatment of the lesion with ethanol sclerotherapy, she suffered acute pulmonary hypertensive crisis. We discuss the pathophysiology of pulmonary hypertension related to ethanol sclerotherapy, and propose that hemolysis plays a significant role. Recommendations for evaluation, monitoring and management of this complication are also discussed.

Congenital Spondylolytic Spondylolisthesis of C2 Vertebra Associated With Atlanto-Axial Dislocation, Chiari Type I Malformation, and Anomalous Vertebral Artery: Case Report With Review Literature.

PubMed

Sardhara, Jayesh; Pavaman, Sindgikar; Das, Kuntal; Srivastava, Arun; Mehrotra, Anant; Behari, Sanjay

2016-11-01

Congenital spondylolytic spondylolisthesis of C2 vertebra resulting from deficient posterior element of the axis is rarely described in the literature. We describe a unique case of agenesis of posterior elements of C2 with craniovertebral junction anomalies consisting of osseous, vascular, and soft tissue anomalies. A 26-year-old man presented with symptoms of upper cervical myelopathy of 12 months' duration. A computed tomography scan of the cervical spine including the craniovertebral junction revealed spondylolisthesis of C2 over C3, atlantoaxial dislocation, occipitalization of the atlas, hypoplasia of the odontoid, and cleft posterior C1 arch. Additionally, the axis vertebra was found devoid of its posterior elements except bilaterally rudimentary pedicles. Magnetic resonance imaging revealed tonsilar herniation, suggesting associated Chiari type I malformation. CT angiogram of the vertebral arteries displayed persistent bilateral first intersegmental arteries crossing the posterior aspect of the C1/2 facet joint. This patient underwent foramen magnum decompression, C3 laminectomy with occipito-C3/C4 posterior fusion using screw and rod to maintain the cervical alignment and stability. We report this rare constellation of congenital craniovertebral junction anomaly and review the relevant literature. Copyright © 2016 Elsevier Inc. All rights reserved.

Sulphonated phthalocyanine induced caudal malformative syndrome in the chick embryo.

PubMed

Sandor, S; Prelipceanu, O; Checiu, I

1985-01-01

Sulphonated phthalocyanine (Pht.) has been tested for its possible noxious effect on the developing chick embryo. When injected into the subembryonic cavity of 40-45 hours incubated chick embryos (mainly 10-20 somite pairs), Pht. induces a highly reproducible caudal malformative syndrome (trunk and taillessness, various anomalies of the limbs). The main effect is--in about 15% of the malformed specimens--associated with unilateral microphthalmy and, less frequently, with coelosomy. Microscopically developmental disturbances of the caudal axial organs, of the mesonephros and of the limbs are observed. The initial pathological changes, at microscopic level, are necrosis and hemorrhages in the caudal axial and paraxial area. The allantois is poorly developed or even absent. Skeletal changes involve anomalies of the ribs and of the vertebral column and total or partial absence of the pelvic girdle bones. The high mortality, mainly during the first week, is due--first of all--to the developmental disturbances including the poor development or absence of the allantois. Control experiments with CuCl2 suggest the ethiological role of Cu. Pathogenetic aspects are discussed.

Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression.

PubMed

Danno, Hiroki; Michiue, Tatsuo; Hitachi, Keisuke; Yukita, Akira; Ishiura, Shoichi; Asashima, Makoto

2008-04-08

The neural-related genes Sox2, Pax6, Otx2, and Rax have been associated with severe ocular malformations such as anophthalmia and microphthalmia, but it remains unclear as to how these genes are linked functionally. We analyzed the upstream signaling of Xenopus Rax (also known as Rx1) and identified the Otx2 and Sox2 proteins as direct upstream regulators of Rax. We revealed that endogenous Otx2 and Sox2 proteins bound to the conserved noncoding sequence (CNS1) located approximately 2 kb upstream of the Rax promoter. This sequence is conserved among vertebrates and is required for potent transcriptional activity. Reporter assays showed that Otx2 and Sox2 synergistically activated transcription via CNS1. Furthermore, the Otx2 and Sox2 proteins physically interacted with each other, and this interaction was affected by the Sox2-missense mutations identified in these ocular disorders. These results demonstrate that the direct interaction and interdependence between the Otx2 and Sox2 proteins coordinate Rax expression in eye development, providing molecular linkages among the genes responsible for ocular malformation.

Salient lesions in domestic ruminants infected with the emerging so-called Schmallenberg virus in Germany.

PubMed

Herder, V; Wohlsein, P; Peters, M; Hansmann, F; Baumgärtner, W

2012-07-01

The so-called Schmallenberg virus (SBV), first detected in a German town of the same name in October 2011, is a novel emerging orthobunyavirus in Europe causing malformations and severe economic loss in ruminants. This report describes lesions in 40 sheep, 2 goats, and 16 cattle naturally infected with SBV as determined by real-time quantitative reverse transcription polymerase chain reaction. The most common macroscopic changes were arthrogryposis, vertebral malformations, brachygnathia inferior, and malformations of the central nervous system, including hydranencephaly, porencephaly, hydrocephalus, cerebellar hypoplasia, and micromyelia. Histologic lesions included lymphohistiocytic meningoencephalomyelitis in some cases, glial nodules mainly in the mesencephalon and hippocampus of lambs and goats, and neuronal degeneration and necrosis mainly in the brain stem of calves. Micromyelia was characterized by a loss of gray and white matter, with few neurons remaining in the ventral horn in calves. The skeletal muscles had myofibrillar hypoplasia in lambs and calves. The lesions of SBV-associated abortion and perinatal death are similar to those attributed to Akabane virus and other viruses in the Simbu group of bunyaviruses.

Long-term outcomes of adults with features of VACTERL association

PubMed Central

Raam, Manu S.; Pineda-Alvarez, Daniel E.; Hadley, Donald W.; Solomon, Benjamin D.

2010-01-01

VACTERL association involves the presence of specific congenital, multi-organ malformations that tend to co-occur. Clinical and research efforts typically center on pediatric patients, and there is a scarcity of information in the literature regarding VACTERL-related issues and outcomes in adulthood. We describe here 11 adults with features of VACTERL association ascertained through our research study on the condition. In our cohort of adult patients, approximately 25% of medically significant malformations that are component features of VACTERL association, including 40% of vertebral, 50% of cardiac, and 50% of renal anomalies, were not identified during childhood. Additionally, medical sequelae of many of the primary malformations identified in infancy or early childhood persist or are first reported in adulthood. These sequelae can involve challenging medical and surgical management in adulthood. As most adults with VACTERL association are not specifically followed for VACTERL-related issues, a more uniform diagnostic work-up and a low threshold for investigation of medical sequelae of the primary disorder may enhance the quality of clinical management in these patients. PMID:20888933

Skeletal morphogenesis of the vertebral column of the miniature hylid frog Acris crepitans, with comments on anomalies.

PubMed

Pugener, L Analía; Maglia, Anne M

2009-01-01

Although the vertebral columns of anurans have received much study in the last 150 years, few detailed descriptions exist of the skeletal morphogenesis of this anatomical unit. Herein, the ontogeny of the vertebral skeleton of the hylid frog Acris crepitans is described based on cleared and double-stained specimens, radiographs, and 3D reconstructions generated from synchrotron microCT scans. The adult axial formula is 1-7-1-1, and the vertebral centra are epichordal and procoelous. The neural arches are nonimbricate, and there is a medial articulation between the laminae of Presacrals I and II. Free ribs are absent. The sacral diapophyses are uniform in width or slightly expanded distally. The urostyle is slender, round in cross section, and about equal in length to the presacral region. Presacral vertebrae are the first to form, developing in a cephalic-to-caudal sequence. However, development and growth are decoupled and growth is fastest initially in the posterior presacrals and sacrum. In addition, there is a time lag between the formation of the presacral/sacral region and the postsacral region. More than 8.5% of the specimens examined have vertebral anomalies, and about 50% display small variants from the typical vertebral column morphology. However, these malformations do not seem to have been so severe as to have affected survival. 2008 Wiley-Liss, Inc.

Chiari type I malformation, syncope, headache, hypoglycemia and hepatic steatosis in an 8-year old girl: a causal association?

PubMed Central

Tarani, Luigi; Del Balzo, Francesca; Costantino, Francesco; Properzi, Enrico; D’Eufemia, Patrizia; Liberati, Natascia; Spalice, Alberto

2010-01-01

Chiari type I malformation (CMI) is a congenital hindbrain anomaly characterized by downward displacement of the cerebellar tonsils through the foramen magnum. Chiari type I malformation often presents with a complex clinical picture and can be sporadic or linked to a variety of genetic conditions. We report on a girl in whom Chiari type I malformation was associated with hypoglycemia, headache, vertigo, syncope and hepatic steatosis. We hypothesize that these symptoms are primarily a consequence of Chiari type I malformation. PMID:21589844

Epigenetic regulation of left-right asymmetry by DNA methylation.

PubMed

Wang, Lu; Liu, Zhibin; Lin, Hao; Ma, Dongyuan; Tao, Qinghua; Liu, Feng

2017-10-16

DNA methylation is a major epigenetic modification; however, the precise role of DNA methylation in vertebrate development is still not fully understood. Here, we show that DNA methylation is essential for the establishment of the left-right (LR) asymmetric body plan during vertebrate embryogenesis. Perturbation of DNA methylation by depletion of DNA methyltransferase 1 ( dnmt1 ) or dnmt3bb.1 in zebrafish embryos leads to defects in dorsal forerunner cell (DFC) specification or collective migration, laterality organ malformation, and disruption of LR patterning. Knockdown of dnmt1 in Xenopus embryos also causes similar defects. Mechanistically, loss of dnmt1 function induces hypomethylation of the lefty2 gene enhancer and promotes lefty2 expression, which consequently represses Nodal signaling in zebrafish embryos. We also show that Dnmt3bb.1 regulates collective DFC migration through cadherin 1 (Cdh1). Taken together, our data uncover dynamic DNA methylation as an epigenetic mechanism to control LR determination during early embryogenesis in vertebrates. © 2017 The Authors.

Klippel-Feil syndrome and Dandy-Walker malformation.

PubMed

Karaman, A; Kahveci, H

2011-01-01

The Klippel-Feil deformity is a complex of osseous and visceral anomalies, which include low hairline, platybasia, fused cervical vertebrae with a short neck, and deafness. Associated central nervous system abnormalities include occipital cephalocele, Chiari I malformation, syrinx, microcephaly, and hydrocephalus. Herein, we report a case with Klippel-Feil syndrome and Dandy-Walker malformation.

Evidence that the notochord may be pivotal in the development of sacral and anorectal malformations.

PubMed

Qi, Bao Quan; Beasley, Spencer W; Frizelle, Francis A

2003-09-01

The notochord is known to organize normal development of central axial structures, such as the spinal cord, vertebral column, and anorectum, but its role in abnormal development of these organs has not been well documented. The current study has used Ethylenethiourea to induce anorectal malformations in fetal rats, allowing investigation of abnormalities of the notochord and their relationship to the axial structural abnormalities that occur. Timed-mated pregnant rats were fed Ethylenethiourea by gavage on gestational day 10. Their embryos were harvested on gestational days 13 to 16 and sectioned in either the transverse or sagittal plane. Sections were stained with H and E and examined serially. Anorectal malformations were identified in 29 of 34 embryos and neural tube defects in 24, ranging from an accessory neural tube to lumbo-sacral rachischisis. There was no tail or only a rudimentary tail in the majority of embryos. Abnormalities of the notochord in the lumbo-sacral area included ventro-dorsal branching, ventral deviation, and ectopic notochordal tissue. Most abnormal notochord branches and ectopic notochordal tissue were abnormally close to or in contact with the wall of the cloaca or neural tube. Given the known role of the notochord in controlling normal development, this study would suggest that abnormal notochord development may be pivotal in producing neural tube defects and anorectal malformations, possibly by altering sonic hedgehog signalling.

Vertebral formula and congenital abnormalities of the vertebral column in rabbits.

PubMed

Proks, P; Stehlik, L; Nyvltova, I; Necas, A; Vignoli, M; Jekl, V

2018-06-01

The aim of this retrospective study of 330 rabbits (164 males, 166 females) was to determine different vertebral formulas and prevalence of congenital vertebral anomalies in rabbits from radiographs of the cervical (C), thoracic (Th), lumbar (L) and sacral (S) segments of the vertebral column. The number of vertebrae in each segment of vertebral column, position of anticlinal vertebra and localisation and type of congenital abnormalities were recorded. In 280/330 rabbits (84.8%) with normal vertebral morphology, seven vertebral formulas were identified: C7/Th12/L7/S4 (252/330, 76.4%), C7/Th12/L6/S4 (11/330, 3.3%), C7/Th13/L7/S4 (8/330, 2.4%), C7/Th12/L7/S5 (4/330, 1.2%), C7/Th12/L8/S4 (3/330, 0.9%), C7/Th12/L7/S6 (1/330, 0.3%) and C7/Th11/L7/S4 (1/330, 0.3%). The anticlinal vertebra was identified as Th10 in 56.4% of rabbits and Th11 in 42.4% of rabbits. Congenital spinal abnormalities were identified in 50/330 (15.2%) rabbits, predominantly as a single pathology (n=44). Transitional vertebrae represented the most common abnormalities (n=41 rabbits) in the thoracolumbar (n=35) and lumbosacral segments (n=6). Five variants of thoracolumbar transitional vertebrae were identified. Cervical butterfly vertebrae were detected in three rabbits. One rabbit exhibited three congenital vertebral anomalies: cervical block vertebra, thoracic hemivertebra and thoracolumbar transitional vertebra. Five rabbits exhibited congenital vertebral abnormalities with concurrent malalignment, specifically cervical kyphosis/short vertebra (n=1), thoracic lordoscoliosis/thoracolumbar transitional vertebrae (n=1), thoracic kyphoscoliosis/wedge vertebrae (n=2) and thoracolumbar lordoscoliosis/thoracolumbar transitional vertebrae/lumbosacral transitional vertebrae (n=1). These findings suggest that vertebral columns in rabbits display a wide range of morphologies, with occasional congenital malformations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ecotoxicology of Amphibians and Reptiles

USGS Publications Warehouse

2000-01-01

For many years, ecological research on amphibians and reptiles has lagged behind that of other vertebrates such as fishes, birds, and mammals, despite the known importance of these animals in their environments. The lack of study has been particularly acute in the he area of ecotoxicology where the number of published scientific papers is a fraction of that found for the other vertebrate classes. Recently, scientists have become aware of severe crises among amphibian populations, including unexplained and sudden extinctions, worldwide declines, and hideous malformations. In many of these instances, contaminants have been listed as probable contributors. Data on the effects of contaminants on reptiles are so depauperate that even the most elementary interpretations are difficult. This state-of-the-science review and synthesis of amphibian and reptile ecotoxicology demonstrates the inter-relationships among distribution, ecology, physiology, and contaminant exposure, and interprets these topics as they pertain to comparative toxicity, population declines, malformations, and risk assessment . In this way, the book identifies and serves as a basis for the most pressing research needs in the coming years. The editors have invited 27 other internationally respected experts to examine the state of existing data in specific areas, interpret it in light of current problems, and identify research gaps and needs. Through its emphasis on recent research, extensive reviews and synthesis, Ecotoxicology of Amphibians and Reptiles will remain a definitive reference work well into the new century.

The zebrafish eye—a paradigm for investigating human ocular genetics

PubMed Central

Richardson, R; Tracey-White, D; Webster, A; Moosajee, M

2017-01-01

Although human epidemiological and genetic studies are essential to elucidate the aetiology of normal and aberrant ocular development, animal models have provided us with an understanding of the pathogenesis of multiple developmental ocular malformations. Zebrafish eye development displays in depth molecular complexity and stringent spatiotemporal regulation that incorporates developmental contributions of the surface ectoderm, neuroectoderm and head mesenchyme, similar to that seen in humans. For this reason, and due to its genetic tractability, external fertilisation, and early optical clarity, the zebrafish has become an invaluable vertebrate system to investigate human ocular development and disease. Recently, zebrafish have been at the leading edge of preclinical therapy development, with their amenability to genetic manipulation facilitating the generation of robust ocular disease models required for large-scale genetic and drug screening programmes. This review presents an overview of human and zebrafish ocular development, genetic methodologies employed for zebrafish mutagenesis, relevant models of ocular disease, and finally therapeutic approaches, which may have translational leads in the future. PMID:27612182

Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression

PubMed Central

Danno, Hiroki; Michiue, Tatsuo; Hitachi, Keisuke; Yukita, Akira; Ishiura, Shoichi; Asashima, Makoto

2008-01-01

The neural-related genes Sox2, Pax6, Otx2, and Rax have been associated with severe ocular malformations such as anophthalmia and microphthalmia, but it remains unclear as to how these genes are linked functionally. We analyzed the upstream signaling of Xenopus Rax (also known as Rx1) and identified the Otx2 and Sox2 proteins as direct upstream regulators of Rax. We revealed that endogenous Otx2 and Sox2 proteins bound to the conserved noncoding sequence (CNS1) located ≈2 kb upstream of the Rax promoter. This sequence is conserved among vertebrates and is required for potent transcriptional activity. Reporter assays showed that Otx2 and Sox2 synergistically activated transcription via CNS1. Furthermore, the Otx2 and Sox2 proteins physically interacted with each other, and this interaction was affected by the Sox2-missense mutations identified in these ocular disorders. These results demonstrate that the direct interaction and interdependence between the Otx2 and Sox2 proteins coordinate Rax expression in eye development, providing molecular linkages among the genes responsible for ocular malformation. PMID:18385377

Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome.

PubMed

Woods, C G; Stricker, S; Seemann, P; Stern, R; Cox, J; Sherridan, E; Roberts, E; Springell, K; Scott, S; Karbani, G; Sharif, S M; Toomes, C; Bond, J; Kumar, D; Al-Gazali, L; Mundlos, S

2006-08-01

Fuhrmann syndrome and the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome are considered to be distinct limb-malformation disorders characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia in humans. In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of chicken mesenchyme cell cultures and developing limbs. The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout). These findings illustrate the specific and conserved importance of WNT7A in multiple aspects of vertebrate limb development.

Mutations in WNT7A Cause a Range of Limb Malformations, Including Fuhrmann Syndrome and Al-Awadi/Raas-Rothschild/Schinzel Phocomelia Syndrome

PubMed Central

Woods, C. G.; Stricker, S.; Seemann, P.; Stern, R.; Cox, J.; Sherridan, E.; Roberts, E.; Springell, K.; Scott, S.; Karbani, G.; Sharif, S. M.; Toomes, C.; Bond, J.; Kumar, D.; Al-Gazali, L.; Mundlos, S.

2006-01-01

Fuhrmann syndrome and the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome are considered to be distinct limb-malformation disorders characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia in humans. In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of chicken mesenchyme cell cultures and developing limbs. The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout). These findings illustrate the specific and conserved importance of WNT7A in multiple aspects of vertebrate limb development. PMID:16826533

Congenital unilateral absence of the upper extremity may give rise to a specific kind of thoracolumbar curve.

PubMed

Olgun, Z Deniz; Demirkiran, Gokhan; Polly, David; Yazici, Muharrem

2018-03-01

There is an increased incidence of scoliosis in patients with congenital malformations of the upper extremity even in the absence of overt vertebral abnormalities. In this case series, we summarize the curve characteristics of four patients presenting to two spine surgery clinics with unilateral amelia or phocomelia and a progressive scoliotic curve with the apex on the side of deficiency. All patients required orthopedic intervention for their curves. Amelia and phocomelia are severe congenital malformations of the upper limb affecting trunk balance and, conceivably, causing scoliosis with the absence of counterbalancing weight on the affected side. The combination of upper limb absence and same-sided scoliosis in these patients may provide a clue of the mechanical factors causing scoliosis in other disorders. In this article, we attempt to define this exceptional deformity, theorize on its etiology, and draw attention to this particular combination of problems. Case series; Level IV.

Mutations in zebrafish pitx2 model congenital malformations in Axenfeld-Rieger syndrome but do not disrupt left-right placement of visceral organs.

PubMed

Ji, Yongchang; Buel, Sharleen M; Amack, Jeffrey D

2016-08-01

Pitx2 is a conserved homeodomain transcription factor that has multiple functions during embryonic development. Mutations in human PITX2 cause autosomal dominant Axenfeld-Rieger syndrome (ARS), characterized by congenital eye and tooth malformations. Pitx2(-/-) knockout mouse models recapitulate aspects of ARS, but are embryonic lethal. To date, ARS treatments remain limited to managing individual symptoms due to an incomplete understanding of PITX2 function. In addition to regulating eye and tooth development, Pitx2 is a target of a conserved Nodal (TGFβ) signaling pathway that mediates left-right (LR) asymmetry of visceral organs. Based on its highly conserved asymmetric expression domain, the Nodal-Pitx2 axis has long been considered a common denominator of LR development in vertebrate embryos. However, functions of Pitx2 during asymmetric organ morphogenesis are not well understood. To gain new insight into Pitx2 function we used genome editing to create mutations in the zebrafish pitx2 gene. Mutations in the pitx2 homeodomain caused phenotypes reminiscent of ARS, including aberrant development of the cornea and anterior chamber of the eye and reduced or absent teeth. Intriguingly, LR asymmetric looping of the heart and gut was normal in pitx2 mutants. These results suggest conserved roles for Pitx2 in eye and tooth development and indicate Pitx2 is not required for asymmetric looping of zebrafish visceral organs. This work establishes zebrafish pitx2 mutants as a new animal model for investigating mechanisms underlying congenital malformations in ARS and high-throughput drug screening for ARS therapeutics. Additionally, pitx2 mutants present a unique opportunity to identify new genes involved in vertebrate LR patterning. We show Nodal signaling-independent of Pitx2-controls asymmetric expression of the fatty acid elongase elovl6 in zebrafish, pointing to a potential novel pathway during LR organogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Challenges in the management of massive intraorbital and hemifacial arteriovenous malformation as causing life-threatening epistaxis.

PubMed

Manuel, Anura Michelle; Kalimuthu, Santhi; Pathmanathan, Sitra Siri; Narayanan, Prepageran; Zainal Abidin, Zurina; Azmi, Khairul; Khalil, Alizan

2017-04-01

Arteriovenous malformations are congenital lesions that may evolve with time and manifest in a plethora of presentations. They can occur as torrential epistaxis when it extensively involves the facial region. Multi-imaging modalities are available to assist in characterizing the structure of the lesion as well as its location and extent. This complex disease requires a multidisciplinary team approach with preoperative embolization and surgery. We present a rare cause of life-threatening epistaxis in a gentleman with a longstanding orbital and hemifacial arteriovenous malformation and discuss the complexities involved in its management. Copyright © 2017. Published by Elsevier Taiwan.

NAD Deficiency, Congenital Malformations, and Niacin Supplementation.

PubMed

Shi, Hongjun; Enriquez, Annabelle; Rapadas, Melissa; Martin, Ella M M A; Wang, Roni; Moreau, Julie; Lim, Chai K; Szot, Justin O; Ip, Eddie; Hughes, James N; Sugimoto, Kotaro; Humphreys, David T; McInerney-Leo, Aideen M; Leo, Paul J; Maghzal, Ghassan J; Halliday, Jake; Smith, Janine; Colley, Alison; Mark, Paul R; Collins, Felicity; Sillence, David O; Winlaw, David S; Ho, Joshua W K; Guillemin, Gilles J; Brown, Matthew A; Kikuchi, Kazu; Thomas, Paul Q; Stocker, Roland; Giannoulatou, Eleni; Chapman, Gavin; Duncan, Emma L; Sparrow, Duncan B; Dunwoodie, Sally L

2017-08-10

Congenital malformations can be manifested as combinations of phenotypes that co-occur more often than expected by chance. In many such cases, it has proved difficult to identify a genetic cause. We sought the genetic cause of cardiac, vertebral, and renal defects, among others, in unrelated patients. We used genomic sequencing to identify potentially pathogenic gene variants in families in which a person had multiple congenital malformations. We tested the function of the variant by using assays of in vitro enzyme activity and by quantifying metabolites in patient plasma. We engineered mouse models with similar variants using the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system. Variants were identified in two genes that encode enzymes of the kynurenine pathway, 3-hydroxyanthranilic acid 3,4-dioxygenase (HAAO) and kynureninase (KYNU). Three patients carried homozygous variants predicting loss-of-function changes in the HAAO or KYNU proteins (HAAO p.D162*, HAAO p.W186*, or KYNU p.V57Efs*21). Another patient carried heterozygous KYNU variants (p.Y156* and p.F349Kfs*4). The mutant enzymes had greatly reduced activity in vitro. Nicotinamide adenine dinucleotide (NAD) is synthesized de novo from tryptophan through the kynurenine pathway. The patients had reduced levels of circulating NAD. Defects similar to those in the patients developed in the embryos of Haao-null or Kynu-null mice owing to NAD deficiency. In null mice, the prevention of NAD deficiency during gestation averted defects. Disruption of NAD synthesis caused a deficiency of NAD and congenital malformations in humans and mice. Niacin supplementation during gestation prevented the malformations in mice. (Funded by the National Health and Medical Research Council of Australia and others.).

Developmental toxicity evaluation of Bendectin in CD rats.

PubMed

Tyl, R W; Price, C J; Marr, M C; Kimmel, C A

1988-06-01

Bendectin, composed of doxylamine succinate and pyridoxine HCl (1:1), is an antinauseant previously prescribed for nausea and vomiting during pregnancy. The present study examined the maternal and developmental effects of Bendectin (0, 200, 500, or 800 mg/kg/day, po) administered to timed-pregnant CD rats (36-41/group) during organogenesis (gestational days [gd] 6-15). At death (gd 20), all live fetuses were examined for external, visceral, and skeletal abnormalities. At 500 and 800 mg/kg/day, maternal toxicity included reduced food consumption during treatment and for the gestation period, increased water consumption in the posttreatment period, reduced weight gain during treatment, and sedation; water consumption was reduced during treatment and for the gestation period, and maternal mortality (17.1%) was observed only at the high dose. Developmental toxicity included reduced prenatal viability (800 mg/kg/day) and reduced fetal body weight/litter (500 and 800 mg/kg/day). In addition, reduced ossification of metacarpals (800 mg/kg/day), phalanges of the forelimbs (500 and 800 mg/kg/day), and of caudal vertebral centra (all doses) was observed. No increase in percent malformed live fetuses/litter was observed. The proportion of litters with one or more malformed fetuses was higher than vehicle controls only at 800 mg/kg/day, with short 13th rib (to which the test species is predisposed) as the predominant observation. By contrast, a positive control agent (nitrofen, 50 mg/kg/day, po, 14 dams) produced 85% malformed fetuses/litter with the predominant malformation being diaphragmatic hernia. In conclusion, the incidence of litters with one or more malformed fetuses was increased only at a dose of Bendectin which produced maternal mortality (17.1%) and other indices of maternal and developmental toxicity (see Discussion).

First record of second-generation facultative parthenogenesis in a vertebrate species, the whitespotted bambooshark Chiloscyllium plagiosum.

PubMed

Straube, N; Lampert, K P; Geiger, M F; Weiß, J D; Kirchhauser, J X

2016-02-01

In this study, two parthenogenetic events within a family of the whitespotted bambooshark Chiloscyllium plagiosum are reported. A captive female produced multiple parthenogens. Unexpectedly, a single specimen of a total of nine parthenogens displayed external claspers characterizing the male sex in chondrichthyans. Upon dissection, internal sexual organs of this specimen were malformed or absent; however, the presence of claspers in this study challenges the as yet assumed sex determination system in this shark species. Even more remarkable was that one of the female parthenogens reproduced asexually again producing viable offspring. As far as is known, this is the first genetically confirmed evidence for second-generation facultative parthenogenesis in vertebrates. These results support the evolutionary significance of parthenogenesis as an alternative to sexual reproduction. © 2016 The Fisheries Society of the British Isles.

Bilateral Internal Carotid Artery Occlusion, External Carotid Artery Stenosis, and Vertebral Artery Kinking: May It Be Asymptomatic?

PubMed

Fatic, Nikola; Jaffer, Usman; Ivana, Saicic; Gordana, Globarevic-Vukcevic; Markovic, Dragan; Kostic, Dusan; Davidovic, Lazar

2017-10-01

The clinical spectrum of internal carotid artery occlusion ranges from being a completely asymptomatic occlusion to a devastating stroke or death. The prevalence of asymptomatic internal carotid artery occlusion is unknown, particularly for bilateral occlusion. The distal branches of the external carotid artery anastomose with distal branches of the internal carotid artery provide important sources of collateral circulation to the brain. Stenosis of the external carotid artery with ipsilateral/bilateral internal occlusion may result in ischemic sequelae. Coiling or kinking of the vertebral artery is a rare morphological entity that is infrequently reported because it remains asymptomatic and has no clinical relevance. Currently, there is little evidence to support management strategies for this disease entity and no official recommendations for asymptomatic bilateral carotid artery occlusion. We present a case of a 62-year-old female with asymptomatic bilateral internal carotid artery occlusion, bilateral external carotid artery stenoses, and bilateral kinking of the vertebral artery at the V2 segment, who has been successfully managed conservatively for over 5 years. An individualized approach to management of patients with bilateral internal carotid artery occlusion, especially in combination with external carotid artery stenosis and elongation malformations of the vertebral artery is key to a successful strategy. Copyright © 2017 Elsevier Inc. All rights reserved.

First-trimester sonographic findings associated with a Dandy-Walker malformation and inferior vermian hypoplasia.

PubMed

Bornstein, Eran; Goncalves Rodríguez, José Luis; Álvarez Pavón, Erika Carolina; Quiroga, Héctor; Or, Drorit; Divon, Michael Y

2013-10-01

We report 2 cases in which first-trimester measurements of the intracranial translucency and the brain stem-to-occipital bone diameter were markedly enlarged. This finding was thought to represent an abnormal fourth ventricle-cisterna magna complex. Subsequently, the diagnoses of a Dandy-Walker malformation with partial vermian agenesis in 1 case and inferior vermian hypoplasia in the other were established and confirmed by either postmortem autopsy or postnatal magnetic resonance imaging. These cases suggest that evaluation of the fourth ventricle-cisterna magna complex, by measuring the intracranial translucency or brain stem-to-occipital bone diameter may identify some cases with structural malformations of the cerebellum as early as the first trimester.

Neural tube defects – disorders of neurulation and related embryonic processes

PubMed Central

Copp, Andrew J.; Greene, Nicholas D. E.

2014-01-01

Neural tube defects (NTDs) are severe congenital malformations affecting 1 in every 1000 pregnancies. ‘Open’ NTDs result from failure of primary neurulation as seen in anencephaly, myelomeningocele (open spina bifida) and craniorachischisis. Degeneration of the persistently open neural tube in utero leads to loss of neurological function below the lesion level. ‘Closed’ NTDs are skin-covered disorders of spinal cord structure, ranging from asymptomatic spina bifida occulta to severe spinal cord tethering, and usually traceable to disruption of secondary neurulation. ‘Herniation’ NTDs are those in which meninges, with or without brain or spinal cord tissue, become exteriorised through a pathological opening in the skull or vertebral column (e.g. encephalocele and meningocele). NTDs have multifactorial etiology, with genes and environmental factors interacting to determine individual risk of malformation. While over 200 mutant genes cause open NTDs in mice, much less is known about the genetic causation of human NTDs. Recent evidence has implicated genes of the planar cell polarity signalling pathway in a proportion of cases. The embryonic development of NTDs is complex, with diverse cellular and molecular mechanisms operating at different levels of the body axis. Molecular regulatory events include the BMP and Sonic hedgehog pathways which have been implicated in control of neural plate bending. Primary prevention of NTDs has been implemented clinically following the demonstration that folic acid, when taken as a peri-conceptional supplement, can prevent many cases. Not all NTDs respond to folic acid, however, and adjunct therapies are required for prevention of this folic acid-resistant category. PMID:24009034

Bone deformities and skeletal malformations in the Roman Imperial Age.

PubMed

Minozzi, Simona; Catalano, Paola; Pantano, Walter; Caldarini, Carla; Fornaciari, Gino

2014-01-01

This paper describes some cases of individuals affected by skeletal deformities resulting in "freak" appearance. The skeletal remains were found during large archaeological excavations in the Roman territory, carried out by the Special Superintendence to the Archeological Heritage of Rome in the last years, dated back to the Imperial Age. The first cases reported are referred to two growth disorders with opposite effects: a case of dwarfism and another of gigantism. The former concerns a young man from the Collatina necropolis with very short and malformed limbs, which allowed a diagnosis of acondroplasic dwarfism, a rare congenital disorder that limits height below 130 cm. The latter case comes from the necropolis of Torre Serpentana in Fidenae, and is instead referred to a young person of very high stature, about 204 cm, suffering from Gigantism, a rare condition which in this case seems to have been linked to a hormonal dysfunction due to a pituitary adenoma. A third case regards a joint disease affecting the vertebral column and causing severe deformities. The skeleton was found in the Collatina necropolis and belongs to an old woman, suffering from ankylosing spondylitis. Finally, the last and very peculiar case is related to an individual recovered in the necropolis of Castel Malnome. The skeletal remains belong to an adult man with a complete fusion of the temporo-mandibular joint, which compromised mastication and caused severe deformation of the maxillofacial complex. These cases are described in detail together with the possible implications that these deformities could have on in the social context.

Vascular malformations: an update.

PubMed

Gloviczki, Peter; Duncan, Audra; Kalra, Manju; Oderich, Gustavo; Ricotta, Joseph; Bower, Thomas; McKusick, Michael; Bjarnason, Haraldur; Driscoll, David

2009-06-01

Vascular malformations occur as a result of an arrest in the development of the vascular system. The modified Hamburg classification distinguishes arterial, venous, arteriovenous, capillary, lymphatic, and mixed vascular malformations. Each malformation is further subdivided based on anatomy and on the time when arrest in development of the embryogenesis occurred; malformations can be truncular or extratruncular. Progress in the last decade in management has been significant because of improvements in open surgical procedures and perfection of percutaneous and hybrid endovascular interventions and devices, such as balloons, stents, and stent-grafts. There has been increasing use of embolization for the treatment of malformations with coils, other particles, glue, or with endovascular placement of occlusive plugs. Absolute alcohol, detergent liquids, or foam have been used for sclerotherapy with improved efficacy. The agents are delivered percutaneously or through a catheter placed either into the feeding arteries or the draining veins. This review aims to aid vascular and endovascular specialists in staying familiar with vascular malformations. These specialists need to be able to evaluate the patients, perform treatment if appropriate, or refer complex cases to multidisciplinary vascular malformation clinics and vascular centers.

A developmental classification of malformations of the brainstem.

PubMed

Barkovich, A James; Millen, Kathleen J; Dobyns, William B

2007-12-01

With advances in imaging and genetics, malformations of the brainstem are being more commonly identified. We describe and classify brainstem anomalies in 138 patients ascertained over a period of 10 years Magnetic resonance imaging studies and, where available, clinical records of the patients were retrospectively reviewed. Malformations were segregated according to magnetic resonance findings and classified when possible by embryological mechanisms The most common location for anomalies was the pons, which was involved in 114 patients. The midbrain was involved in 45 patients, whereas the medulla was involved in 14. In 53 patients, more than 1 region was affected (all 3 regions in 6 patients, midbrain and pons in 39, and medulla and pons in 8). The malformations were divided into four groups: (1) malformations with abnormal brainstem segmentation, (2) malformations with segmental hypoplasia, (3) postsegmentation malformations, and (4) malformations associated with abnormal cortical organization The malformations of the brainstem identified in this study were diverse and complex. This proposed classification organizes them into groupings based on known genetics and embryological events. Use of this system will help clinicians and scientists to better understand these disorders and, ultimately, to better counsel families of affected patients.

The PTK7-Related Transmembrane Proteins Off-track and Off-track 2 Are Co-receptors for Drosophila Wnt2 Required for Male Fertility

PubMed Central

Honemann-Capito, Mona; Brechtel-Curth, Katja; Hedderich, Marie; Wodarz, Andreas

2014-01-01

Wnt proteins regulate many developmental processes and are required for tissue homeostasis in adult animals. The cellular responses to Wnts are manifold and are determined by the respective Wnt ligand and its specific receptor complex in the plasma membrane. Wnt receptor complexes contain a member of the Frizzled family of serpentine receptors and a co-receptor, which commonly is a single-pass transmembrane protein. Vertebrate protein tyrosine kinase 7 (PTK7) was identified as a Wnt co-receptor required for control of planar cell polarity (PCP) in frogs and mice. We found that flies homozygous for a complete knock-out of the Drosophila PTK7 homolog off track (otk) are viable and fertile and do not show PCP phenotypes. We discovered an otk paralog (otk2, CG8964), which is co-expressed with otk throughout embryonic and larval development. Otk and Otk2 bind to each other and form complexes with Frizzled, Frizzled2 and Wnt2, pointing to a function as Wnt co-receptors. Flies lacking both otk and otk2 are viable but male sterile due to defective morphogenesis of the ejaculatory duct. Overexpression of Otk causes female sterility due to malformation of the oviduct, indicating that Otk and Otk2 are specifically involved in the sexually dimorphic development of the genital tract. PMID:25010066

The PTK7-related transmembrane proteins off-track and off-track 2 are co-receptors for Drosophila Wnt2 required for male fertility.

PubMed

Linnemannstöns, Karen; Ripp, Caroline; Honemann-Capito, Mona; Brechtel-Curth, Katja; Hedderich, Marie; Wodarz, Andreas

2014-07-01

Wnt proteins regulate many developmental processes and are required for tissue homeostasis in adult animals. The cellular responses to Wnts are manifold and are determined by the respective Wnt ligand and its specific receptor complex in the plasma membrane. Wnt receptor complexes contain a member of the Frizzled family of serpentine receptors and a co-receptor, which commonly is a single-pass transmembrane protein. Vertebrate protein tyrosine kinase 7 (PTK7) was identified as a Wnt co-receptor required for control of planar cell polarity (PCP) in frogs and mice. We found that flies homozygous for a complete knock-out of the Drosophila PTK7 homolog off track (otk) are viable and fertile and do not show PCP phenotypes. We discovered an otk paralog (otk2, CG8964), which is co-expressed with otk throughout embryonic and larval development. Otk and Otk2 bind to each other and form complexes with Frizzled, Frizzled2 and Wnt2, pointing to a function as Wnt co-receptors. Flies lacking both otk and otk2 are viable but male sterile due to defective morphogenesis of the ejaculatory duct. Overexpression of Otk causes female sterility due to malformation of the oviduct, indicating that Otk and Otk2 are specifically involved in the sexually dimorphic development of the genital tract.

Synaptic scaffold evolution generated components of vertebrate cognitive complexity

PubMed Central

Nithianantharajah, J.; Komiyama, N.H.; McKechanie, A.; Johnstone, M.; Blackwood, D. H.; St Clair, D.; Emes, R.D.; van de Lagemaat, L. N.; Saksida, L.M.; Bussey, T.J.; Grant, S.G.N.

2014-01-01

The origins and evolution of higher cognitive functions including complex forms of learning, attention and executive functions are unknown. A potential mechanism driving the evolution of vertebrate cognition early in the vertebrate lineage (550 My ago) was genome duplication and subsequent diversification of postsynaptic genes. Here we report the first genetic analysis of a vertebrate gene family in cognitive functions measured using computerized touchscreens. Comparison of mice carrying mutations in all four Dlg paralogs show simple associative learning required Dlg4, while Dlg2 and Dlg3 diversified to play opposing roles in complex cognitive processes. Exploiting the translational utility of touchscreens in humans and mice, testing Dlg2 mutations in both species showed Dlg2’s role in complex learning, cognitive flexibility and attention has been highly conserved over 100 My. Dlg family mutations underlie psychiatric disorders suggesting genome evolution expanded the complexity of vertebrate cognition at the cost of susceptibility to mental illness. PMID:23201973

Examination of a Palatogenic Gene Program in Zebrafish

PubMed Central

Swartz, Mary E.; Sheehan-Rooney, Kelly; Dixon, Michael J.; Eberhart, Johann K.

2011-01-01

Human palatal clefting is debilitating and difficult to rectify surgically. Animal models enhance our understanding of palatogenesis and are essential in strategies designed to ameliorate palatal malformations in humans. Recent studies have shown that the zebrafish palate, or anterior neurocranium, is under similar genetic control to the amniote palatal skeleton. We extensively analyzed palatogenesis in zebrafish to determine the similarity of gene expression and function across vertebrates. By 36 hpf palatogenic cranial neural crest cells reside in homologous regions of the developing face compared to amniote species. Transcription factors and signaling molecules regulating mouse palatogenesis are expressed in similar domains during palatogenesis in zebrafish. Functional investigation of a subset of these genes, fgf10a, tgfb2, pax9 and smad5 revealed their necessity in zebrafish palatogenesis. Collectively, these results suggest that the gene regulatory networks regulating palatogenesis may be conserved across vertebrate species, demonstrating the utility of zebrafish as a model for palatogenesis. PMID:22016187

Beckwith-Wiedemann syndrome and Chiari I malformation--a case-based review of central nervous system involvement in hemihypertrophy syndromes.

PubMed

Udayakumaran, Suhas; Onyia, Chiazor U

2015-05-01

Beckwith-Wiedemann syndrome (BWS) is an unusual complex of abnormalities that includes mainly omphalocele, macroglossia, gigantism, visceromegaly, and neonatal hypoglycemia. Type I Chiari malformation, on the other hand, is defined as ectopia of the cerebellar tonsils below the plane of the foramen magnum. Only one case of association of BWS with Chiari I malformation has been previously reported in the literature. Several conditions involving congenital hemihypertrophy have been previously reported in association with Type I Chiari malformation. The pathophysiological mechanism for most of these associations is thought to be quite complex and still remains unclear. However, the presence of tonsillar herniation in BWS has been explained by Tubbs and Oakes in the only one existing case report of BWS with Type I Chiari malformation in the literature, to be due to associated hemihypertrophy of the skull base. We additionally suggest that cerebellar hypertrophy may also contribute to the tonsillar herniation and fourth ventricular outlet obstruction. We now report our recent experience on this association following a review of the literature on association of other hemihypertrophy syndromes with the central nervous system anomalies. We believe that a common pathogenesis of Type I Chiari malformation occurs in conditions of hemihypertrophy including BWS, probably secondary to dysmorphology involving the posterior cranial fossa, and is not just an associated finding.

Cerebellar and Brainstem Malformations.

PubMed

Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

2016-08-01

The frequency and importance of the evaluation of the posterior fossa have increased significantly over the past 20 years owing to advances in neuroimaging. Conventional and advanced neuroimaging techniques allow detailed evaluation of the complex anatomic structures within the posterior fossa. A wide spectrum of cerebellar and brainstem malformations has been shown. Familiarity with the spectrum of cerebellar and brainstem malformations and their well-defined diagnostic criteria is crucial for optimal therapy, an accurate prognosis, and correct genetic counseling. This article discusses cerebellar and brainstem malformations, with emphasis on neuroimaging findings (including diagnostic criteria), neurologic presentation, systemic involvement, prognosis, and recurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

Achondroplasia and Macular Coloboma.

PubMed

Ahoor, M H; Amizadeh, Y; Sorkhabi, R

2015-01-01

Achondroplasia is an autosomal dominant congenital disorder of enchondral ossification. It is clinically characterized by low stature, craniofacial deformity, and vertebral malformation. Associated ophthalmic features include telecanthus, exotropia, angle anomalies, and cone-rod dystrophy. A 24-year-old male presented with decreased vision bilaterally and typical achondroplasia. The best corrected visual acuity was 20/70 in both eyes. Anterior segment examination was normal. Fundus examination revealed a well-demarcated circular paramacular lesion in both eyes. As macular coloboma and achondroplasia are developmental disorders, the funduscopic examination is required in patients with achondroplasia.

Achondroplasia and Macular Coloboma

PubMed Central

Ahoor, M. H.; Amizadeh, Y.; Sorkhabi, R.

2015-01-01

Achondroplasia is an autosomal dominant congenital disorder of enchondral ossification. It is clinically characterized by low stature, craniofacial deformity, and vertebral malformation. Associated ophthalmic features include telecanthus, exotropia, angle anomalies, and cone-rod dystrophy. A 24-year-old male presented with decreased vision bilaterally and typical achondroplasia. The best corrected visual acuity was 20/70 in both eyes. Anterior segment examination was normal. Fundus examination revealed a well-demarcated circular paramacular lesion in both eyes. As macular coloboma and achondroplasia are developmental disorders, the funduscopic examination is required in patients with achondroplasia. PMID:26692730

A previously unreported, dominantly inherited syndrome of shortness of stature, ear malformations, and hip dislocation: the coxoauricular syndrome--autosomal or X-linked male-lethal.

PubMed

Duca, D; Pană, I; Ciovirnache, M; Simionesu, L; Ispas, I; Maxililian, C

1981-01-01

We reported an apparently previously undescribed syndrome, designated the coxoauricular syndrome, in a mother and her 3 daughters, all of whom shared in variable manner shortness of stature, minor vertebral and pelvic changes, dislocated hip(s), and microtia with corresponding hearing loss. The oldest daughter had coincidental Ullrich-Turner syndrome with 46, Xdel(X)(q 13) chromosome constitution. Inheritance of the trait in this family is dominant, either autosomal or X-linked, with hemizygote lethality.

Tracheal Atresia with Segmental Esophageal Duplication: An Unusual Anatomic Arrangement.

PubMed

Gaerty, Kirsten; Thomas, Joseph T; Petersen, Scott; Tan, Edwin; Kumar, Sailesh; Gardener, Glenn; Armes, Jane

2016-01-01

An unusual anatomic configuration of segmental tracheal agenesis/atresia with esophageal duplication on autopsy in a fetus that demised in utero at 29 weeks is reported. The mother was scanned initially for a cardiac anomaly at 20 weeks and on follow-up scan at 27 weeks had polyhydramnios and underwent amnioreduction. The final autopsy diagnosis was vertebral, ano-rectal, cardiac, tracheoesophageal, renal, and limb malformations (VACTERL). We discuss the autopsy findings along with the embryological mechanisms and compare the configuration with Floyd's classification for tracheal agenesis. The difficulties in prenatal diagnosis are discussed.

Teratogenic effects of 4-nonylphenol on early embryonic and larval development of the catfish Heteropneustes fossilis.

PubMed

Chaube, Radha; Gautam, Geeta J; Joy, Keerikattil P

2013-05-01

Alkylphenol polyethoxylates (APEs), which are widely used in detergents, paints, herbicides, insecticides, and in many other formulations, have been widely detected in aquatic environments. 4-Nonylphenol (NP) is an important APE detected at microgram levels per litre (0.1-336 μg/L) in water. The objective of the present study was to evaluate NP's toxic effects at low and high sublethal concentrations (0.1 and 1 μg/L) on embryonic development of the catfish Heteropneustes fossilis at different time intervals. The data show that fertilization rate was decreased and cleavage and blastula were severely affected leading to complete mortality of embryos. NP exposure resulted in various body malformations in larvae, such as vertebral deformations, e.g., fin blistering/necrosis, axial deformities (lordosis, kyphosis, and scoliosis) of the spine in the abdominal and caudal region, tail curved completely backward, shortened body, severe spinal and yolk sac malformations, C-shaped severe spinal curvature, cranial malformation with undeveloped head, and failure of eye development. The level of body malformations increased with the concentration and exposure time. After 72 h of exposure, all larvae were dead at both concentrations. Scanning electron microscope study showed that epidermal cells (keratinocytes) were severely damaged in both low- and high-dose treatments throughout development, leading to development of numerous depressions representing sinking holes on the skin. Mucous glands increased significantly in treatment groups compared with control groups. The present study highlights the severe teratogenic effects of NP. The prevalence of the contaminant, if not checked, can lead to decreased population and ultimate disappearance of the species.

Clinical Geneticists’ Views of VACTERL/VATER Association

PubMed Central

Solomon, Benjamin D.; Bear, Kelly A.; Kimonis, Virginia; de Klein, Annelies; Scott, Daryl A.; Shaw-Smith, Charles; Tibboel, Dick; Reutter, Heiko; Giampietro, Philip F.

2012-01-01

VACTERL association (sometimes termed “VATER association” depending on which component features are included) is typically defined by the presence of at least three of the following congenital malformations, which tend to statistically co-occur in affected individuals: Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, and Limb abnormalities. Although the clinical criteria for VACTERL association may appear to be straightforward, there is wide variability in the way clinical geneticists define the disorder and the genetic testing strategy they use when confronted with an affected patient. In order to describe this variability and determine the most commonly used definitions and testing modalities, we present the results of survey responses by 121 clinical geneticists. We discuss the results of the survey responses, provide a literature review and commentary from a group of physicians who are currently involved in clinical and laboratory-based research on VACTERL association, and offer an algorithm for genetic testing in patients with this association. PMID:23165726

A Curriculum Vitae of Teeth: Evolution, Generation, Regeneration

PubMed Central

Koussoulakou, Despina S.; Margaritis, Lukas H.; Koussoulakos, Stauros L.

2009-01-01

The ancestor of recent vertebrate teeth was a tooth-like structure on the outer body surface of jawless fishes. Over the course of 500,000,000 years of evolution, many of those structures migrated into the mouth cavity. In addition, the total number of teeth per dentition generally decreased and teeth morphological complexity increased. Teeth form mainly on the jaws within the mouth cavity through mutual, delicate interactions between dental epithelium and oral ectomesenchyme. These interactions involve spatially restricted expression of several, teeth-related genes and the secretion of various transcription and signaling factors. Congenital disturbances in tooth formation, acquired dental diseases and odontogenic tumors affect millions of people and rank human oral pathology as the second most frequent clinical problem. On the basis of substantial experimental evidence and advances in bioengineering, many scientists strongly believe that a deep knowledge of the evolutionary relationships and the cellular and molecular mechanisms regulating the morphogenesis of a given tooth in its natural position, in vivo, will be useful in the near future to prevent and treat teeth pathologies and malformations and for in vitro and in vivo teeth tissue regeneration. PMID:19266065

Heparan Sulfate Expression in the Neural Crest is Essential for Mouse Cardiogenesis

PubMed Central

Pan, Yi; Carbe, Christian; Pickhinke, Ute; Kupich, Sabine; Ohlig, Stefanie; Frye, Maike; Seelige, Ruth; Pallerla, Srinivas R.; Moon, Anne M.; Lawrence, Roger; Esko, Jeffrey D.; Zhang, Xin; Grobe, Kay

2015-01-01

Impaired heparan sulfate (HS) synthesis in vertebrate development causes complex malformations due to the functional disruption of multiple HS-binding growth factors and morphogens. Here, we report developmental heart defects in mice bearing a targeted disruption of the HS-generating enzyme GlcNAc N-Deacetylase/GlcN N-Sulfotransferase 1 (NDST1), including ventricular septal defects (VSD), persistent truncus arteriosus (PTA), double outlet right ventricle (DORV), and retroesophageal right subclavian artery (RERSC). These defects closely resemble cardiac anomalies observed in mice made deficient in the cardiogenic regulator fibroblast growth factor 8 (FGF8). Consistent with this, we show that HS-dependent FGF8/FGF-receptor2C assembly and FGF8-dependent ERK-phosphorylation are strongly reduced in NDST1−/− embryonic cells and tissues. Moreover, WNT1-Cre/LoxP-mediated conditional targeting of NDST function in neural crest cells (NCCs) revealed that their impaired HS-dependent development contributes strongly to the observed cardiac defects. These findings raise the possibility that defects in HS biosynthesis may contribute to congenital heart defects in humans that represent the most common type of birth defect. PMID:24200809

Incidence and impact of axial malformations in larval bullfrogs (Rana catesbeiana) developing in sites polluted by a coal-burning power plant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hopkins, W.A.; Congdon, J.; Ray, J.K.

2000-04-01

Amphibian malformations have recently received much attention from the scientific community, but few studies have provided evidence linking environmental pollution to larval amphibian malformations in the field. The authors document an increased incidence of axial malformations in bullfrog larvae (Rana catesbeiana) inhabiting two sites contaminated with coal combustion wastes. In the polluted sites, 18 and 37% of larvae exhibited lateral curvatures of the spine, whereas zero and 4% of larvae from two reference sites had similar malformations. Larvae from the most heavily polluted site had significantly higher tissue concentrations of potentially toxic trace elements, including As, Cd, Se, Cu, Cr,more » and V, compared with conspecifics from the reference sites. In addition, malformed larvae from the cost contaminated site had decreased swimming speeds compared with those of normal larvae from the same site. The authors hypothesize that the complex mixture of contaminants produced by coal combustion is responsible for the high incidence of malformations and associated effects on swimming performance.« less

Ablation of Mrds1/Ofcc1 Induces Hyper-γ-Glutamyl Transpeptidasemia without Abnormal Head Development and Schizophrenia-Relevant Behaviors in Mice

PubMed Central

Ohnishi, Tetsuo; Yamada, Kazuo; Watanabe, Akiko; Ohba, Hisako; Sakaguchi, Toru; Honma, Yota; Iwayama, Yoshimi; Toyota, Tomoko; Maekawa, Motoko; Watanabe, Kazutada; Detera-Wadleigh, Sevilla D.; Wakana, Shigeharu; Yoshikawa, Takeo

2011-01-01

Mutations in the Opo gene result in eye malformation in medaka fish. The human ortholog of this gene, MRDS1/OFCC1, is a potentially causal gene for orofacial cleft, as well as a susceptibility gene for schizophrenia, a devastating mental illness. Based on this evidence, we hypothesized that this gene could perform crucial functions in the development of head and brain structures in vertebrates. To test this hypothesis, we created Mrds1/Ofcc1-null mice. Mice were examined thoroughly using an abnormality screening system referred to as “the Japan Mouse Clinic”. No malformations of the head structure, eye or other parts of the body were apparent in these knockout mice. However, the mutant mice showed a marked increase in serum γ-glutamyl transpeptidase (GGT), a marker for liver damage, but no abnormalities in other liver-related measurements. We also performed a family-based association study on the gene in schizophrenia samples of Japanese origin. We found five single nucleotide polymorphisms (SNPs) located across the gene that showed significant transmission distortion, supporting a prior report of association in a Caucasian cohort. However, the knockout mice showed no behavioral phenotypes relevant to schizophrenia. In conclusion, disruption of the Mrds1/Ofcc1 gene elicits asymptomatic hyper-γ-glutamyl-transpeptidasemia in mice. However, there were no phenotypes to support a role for the gene in the development of eye and craniofacial structures in vertebrates. These results prompt further examination of the gene, including its putative contribution to hyper-γ-glutamyl transpeptidasemia and schizophrenia. PMID:22242126

Concomitant intramedullary arteriovenous malformation and a vertebral hemangioma of cervical spine discovered by a pathologic fracture during bicycle accident.

PubMed

Ayhan, Selim; Palaoglu, Selcuk; Geyik, Serdar; Saatci, Isil; Onal, Mehmet Bulent

2015-01-01

Spinal intramedullary arteriovenous malformations are uncommon and a challenging type of neurosurgical entities. They are rarely located to cervical segment. On the other hand, although hemangiomas are relatively common bone tumors, cervical involvement is again rare and clinically significant ones are infrequent. A 14 year-old-male patient referred to an academic tertiary care unit and presented with neck pain and left hand weakness. Neurological examination revealed motor strength deficit at intrinsic muscles and hyperesthesia at the left hand. Furthermore the pathological reflexes were positive on the left hand side. Imaging studies showed compression fracture, lytic changes resembling a hemangioma at C7 vertebra, and also an intramedullary vascular pathology at C5-6 level which was shown to be an intradural-intramedullary arteriovenous malformation (AVM) on digital subtraction angiography. Based on neurological and radiological findings, the decision was to treat the patient. After embolization of the AVM, the neurological condition of the patient deteriorated and immediate MRI scan of the cervical spine revealed edema of the spinal cord at the C5-6 level. Thus an emergent surgery was performed and C5-6-7 laminectomies with C5-T2 posterior fixation and arthrodesis were implemented. A second stage operation was carried out as C7 corpectomy with a distractable titanium cage 2 weeks after initial surgery. A follow-up evaluation at five years revealed 4/5 motor strength on his left intrinsic hand muscles and mild hyperactive deep tendon reflexes. Imaging studies at the postoperative period showed stable placement of the construct and no evidence of contrast enhancement at the C5-6 level inside the spinal cord. A rare case of multiple pathologies affecting the cervical spine, coincidentally diagnosed after a pathological fracture during a bicycle accident as vertebral hemangioma and intradural-intramedullary AVM that was successfully treated with early detection, have been presented. One should assess such patients under multidisciplinary fashion and treat on a case-by-case basis for achieving the best results in patient care.

Factors associated with frequency of abortions recorded through Dairy Herd Improvement test plans.

PubMed

Norman, H D; Miller, R H; Wright, J R; Hutchison, J L; Olson, K M

2012-07-01

Frequency of abortions recorded through Dairy Herd Improvement (DHI) testing was summarized for cows with lactations completed from 2001 through 2009. For 8.5 million DHI lactations of cows that had recorded breeding dates and were >151 d pregnant at lactation termination, the frequency of recorded abortions was 1.31%. Effects of year, herd-year, month, and pregnancy stage at lactation termination; parity; breed; milk yield; herd size; geographic region; and state within region associated with DHI-recorded abortion were examined. Abortions recorded through DHI (minimum gestation of 152 d required) were more frequent during early gestation; least squares means (LSM) were 4.38, 3.27, 1.19, and 0.59% for 152 to 175, 176 to 200, 201 to 225, and 226 to 250 d pregnant, respectively. Frequency of DHI-recorded abortions was 1.40% for parity 1 and 1.01% for parity ≥ 8. Abortion frequency was highest from May through August (1.42 to 1.53%) and lowest from October through February (1.09 to 1.21%). Frequency of DHI-recorded abortions was higher for Holsteins (1.32%) than for Jerseys (1.10%) and other breeds (1.27%). Little relationship was found between DHI-recorded abortions and herd size. Abortion frequencies for effects should be considered to be underestimated because many abortions, especially those caused by genetic recessives, go undetected. Therefore, various nonreturn rates (NRR; 60, 80, …, 200 d) were calculated to document pregnancy loss confirmed by the absence of homozygotes in the population. Breeding records for April 2011 US Department of Agriculture sire conception rate evaluations were analyzed with the model used for official evaluations with the addition of an interaction between carrier status of the service sire (embryo's sire) and cow sire (embryo's maternal grandsire). Over 13 million matings were examined using various NRR for Holstein lethal recessive traits (brachyspina and complex vertebral malformation) and undesirable recessive haplotypes (HH1, HH2, and HH3) as well as >61,000 matings for a Brown Swiss haplotype (BH1), and 670,000 matings for a Jersey haplotype (JH1). Over 80% of fertility loss occurred by 60 d after breeding for BH1, HH3, and JH1, by 80 d for HH2, by 100 d for BY, and by 180 d for HH1. For complex vertebral malformation, fertility loss increased from 40 to 74% across gestation. Association of undesirable recessives with DHI-recorded abortions ranged from 0.0% for Jerseys to 2.4% for Holsteins. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Recurrent High-Flow Arterio-Venous Malformation of the Thyroid Gland.

PubMed

Borchert, D H; Massmann, A; Kim, Y J; Bader, C A; Wolf, G; Eisele, R; Minko, P; Bücker, A; Glanemann, M

2015-09-01

Vascular malformations and hemangiomas of the thyroid gland are rare disorders. The first case of a patient with recurrent high-flow arterio-venous malformation of the right thyroid gland involving the right endolarynx is presented. In June 2013, a 42-year-old female patient presented to the surgical department with recurrent hoarseness and a soft, vibrating mass on the right side of her neck. In 1993, she underwent right subtotal hemithyroidectomy with embolization on the day before surgery for a high-flow arterio-venous malformation of the thyroid gland. Diagnostic work-up in 2013 demonstrated a complex recurrent high-flow arterio-venous malformation on the right side of her neck involving the endolarynx. Full function of the right vocal fold could not be ascertained. The lesion was embolized again and excised the following day. Intraoperative gross bleeding and scar tissue prevented visualization and monitoring of the recurrent laryngeal nerve. Gross bleeding was also noted on hemithyroidectomy after embolization in 1993. No therapy was needed for the endolaryngeal part of the lesion. Histology showed large arterio-venous malformations with thyroid tissue. She remains well without signs of recurrence 18 month later but with a definitive voice handicap. This is the first report of a recurrent high-flow arterio-venous malformation originally developing from the right thyroid gland involving the right endolarynx. Counseling, diagnostic, and therapeutic work-up of the patient was possible only with an interdisciplinary team. The endolaryngeal part of the hemangioma dried out after embolization and completion hemithyroidectomy. Her hoarseness has greatly improved but a definitive voice handicap remains. High-flow arterio-venous malformations of the thyroid gland are a rare disease, and recurrent lesions have not been reported. Interdisciplinary management of these patients is mandatory due to the complex nature of the underlying pathology. Recurrence might develop after long free intervals.

Biological Concerns on the Selection of Animal Models for Teratogenic Testing.

PubMed

Alves-Pimenta, Sofia; Colaço, Bruno; Oliveira, Paula A; Venâncio, Carlos

2018-01-01

During pregnancy fetus can be exposed to a variety of chemicals which may induce abortion and malformations. Due to the amounts of new substances coming into the market every year, a high demand for a rapid, reliable, and cost-effective method to detect potential toxicity is necessary. Different species have been used as animal models for teratogen screening, most of them sharing similar development processes with humans. However, the application of embryology knowledge to teratology is hampered by the complexity of the reproduction processes.The present chapter outlines the essential development periods in different models, and highlights the similarities and differences between species, advantages and disadvantages of each group, and specific sensitivities for teratogenic tests. These models can be organized into the following categories: (1) invertebrate species such Caenorhabditis elegans and Drosophila melanogaster, which have become ideal for screening simple mechanisms in the early periods of reproductive cycle, allowing for rapid results and minor ethical concerns; (2) vertebrate nonmammalian species such Xenopus laevis and Danio rerio, important models to assess teratogenic potential in later development with fewer ethical requirements; and (3) the mammalian species Mus musculus, Rattus norvegicus, and Oryctolagus cuniculus, phylogenetically more close to humans, essential to assess complex specialized processes, that occur later in development.Rules for development toxicology tests require the use of mammalian species. However, ethical concerns and costs limit their use in large-scale screening. By contrast, invertebrate and vertebrate nonmammalian species are increasing as alternative animal models, as these organisms combine less ethical requirements, low costs and culture conditions compatible with large-scale screening. In contrast to the in vitro techniques, their main advantage is to allow for high-throughput screening in a whole-animal context, not dependent on the prior identification of a target. In this chapter, the biological development of the animals most used in teratogenic tests is adressed with the aims of maximizing human translation, reducing the number of animals used, and the time to market for new drugs.

Cranioschisis aperta with encephaloschisis in cephalothoracopagus hamster twins.

PubMed Central

Willhite, C C; Rossi, N L; Frakes, R A; Sharma, R P

1985-01-01

The results of gross and histopathological study of a near-term male hamster exencephalic lateral cephalothoracopagus are presented. There was minimal duplication of the internal organs to the point of division at the abdomen. The appendicular skeleton was relatively unaffected by the severe malformations of the axial skeleton. The studies suggested that the lateral relationship of the skull to the spinal columns was a consequence of the presence of two embryonic neural tubes; the chordomesodermal systems of the right and left twins apparently contributed the tissues for the right and left cephalic neural folds, respectively. Anomalies of the vertebral bodies and neural arches were not related to failure of closure of the neural tube as there was no evidence for rachischisis in either body half. Rather, the anomalous axial skeletal elements were apparently the result of competing fields of development by two chordomesodermal systems. The twins were recovered from a dam maintained on a diet consisting of 80% cassava, a cyanide-containing staple consumed by humans in tropical countries. Because the numbers of resorbed implantation sites and malformed litermates were low and the failure to produce conjoined twins in other litters recovered from dams given cassava diets, it appears unlikely that the malformation was related to the composition of the diet. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. PMID:4016585

The prevalence of lumbar spondylolysis in young children: a retrospective analysis using CT.

PubMed

Lemoine, Thibaut; Fournier, Joseph; Odent, Thierry; Sembély-Taveau, Catherine; Merenda, Pauline; Sirinelli, Dominique; Morel, Baptiste

2018-05-01

Although lumbar spondylolysis is encountered in general population with an incidence estimated to be 3-10%, limited information is available for children. The aim of the study is to determine the prevalence of spondylolysis according to associated vertebral bony malformation and spinopelvic parameters in children under eight requiring CT evaluation for unrelated lumbar conditions. Seven hundred and seventeen abdominal and pelvic multi-detector CT scans were obtained in patients under 8 years of age were reviewed. Two board certificated radiologists and two resident radiologists retrospectively evaluated CT scans for lumbar spondylolysis and associated malformations. Pelvic incidence and spondylolisthesis were reported. Our analysis included 717 CT scans in 532 children (259 girls and 273 boys). Twenty-five cases of spondylolysis were diagnosed (16 bilateral and 9 unilateral, 64 and 36%, respectively) in 14 boys (56%) and 11 girls (44%), associating with 12 grade I spondylolisthesis. The mean normal pelvic incidence was 45° (median 44°, SD 7°). The prevalence of spondylolysis was 1% in children under age 3 (n = 3 among 292 patients), 3.7% in children under age 6 (n = 17 among 454 patients) and 4.7% among the 532 patients. Unilateral spondylolysis was significantly associated with a spinal malformation (p = 0.04, Fisher's exact test), with normal pelvic incidence. Half of the patients with bilateral spondylolysis had high pelvic incidence. We observed a prevalence peak of unilateral spondylolysis in the context of a specific malformation in young infants under age 4 with normal pelvic incidence, and, then, a progressive increase in the prevalence of bilateral isolated spondylolysis.

Rare association of anophthalmia, complex congenital heart disease and pulmonary hypertension: case report.

PubMed

Ríos-Méndez, Raúl Enrique; Lozano Chinga, Michell Marola

2016-10-07

Clinical congenital anophthalmia is described as the uni- or bilateral absence of the eyeball that might occur in isolation or as part of a syndrome. It has a very low prevalence and its etiology is heterogeneous. Complex congenital cardiac malformations are also rare. The association of congenital anophthalmia and congenital heart disease is rarer still, and the etiology of those associations is not well understood yet. We report the case of a patient who had the very rare association of bilateral anophthalmia, multiple cardiac malformations and severe pulmonary hypertension.

Operative management of brainstem cavernous malformations.

PubMed

Asaad, Wael F; Walcott, Brian P; Nahed, Brian V; Ogilvy, Christopher S

2010-09-01

Brainstem cavernous malformations (CMs) are complex lesions associated with hemorrhage and neurological deficit. In this review, the authors describe the anatomical nuances relating to the operative techniques for these challenging lesions. The resection of brainstem CMs in properly selected patients has been demonstrated to reduce the risk of rehemorrhage and can be achieved relatively safely in experienced hands.

Specification of jaw identity by the Hand2 transcription factor

PubMed Central

Funato, Noriko; Kokubo, Hiroki; Nakamura, Masataka; Yanagisawa, Hiromi; Saga, Yumiko

2016-01-01

Acquisition of the lower jaw (mandible) was evolutionarily important for jawed vertebrates. In humans, syndromic craniofacial malformations often accompany jaw anomalies. The basic helix-loop-helix transcription factor Hand2, which is conserved among jawed vertebrates, is expressed in the neural crest in the mandibular process but not in the maxillary process of the first branchial arch. Here, we provide evidence that Hand2 is sufficient for upper jaw (maxilla)-to-mandible transformation by regulating the expression of homeobox transcription factors in mice. Altered Hand2 expression in the neural crest transformed the maxillae into mandibles with duplicated Meckel’s cartilage, which resulted in an absence of the secondary palate. In Hand2-overexpressing mutants, non-Hox homeobox transcription factors were dysregulated. These results suggest that Hand2 regulates mandibular development through downstream genes of Hand2 and is therefore a major determinant of jaw identity. Hand2 may have influenced the evolutionary acquisition of the mandible and secondary palate. PMID:27329940

Aggressive vertebral hemangioma of the thoracic spine without typical radiological appearance.

PubMed

Dang, Lei; Liu, Chen; Yang, Shao Min; Jiang, Liang; Liu, Zhong Jun; Liu, Xiao Guang; Yuan, Hui Shu; Wei, Feng; Yu, Miao

2012-10-01

Vertebral hemangioma (VH) is virtually vascular malformation, which is usually asymptomatic. Only 3.7 % of VH may become active and symptomatic, and 1 % may invade the spinal canal and/or paravertebral space. Treatment protocols for active or aggressive VHs are still in controversy. Reported treatments include radiotherapy, vertebroplasty, direct alcohol injection, embolization, surgery and a combination of these modalities. A 41-year-old lady was presented with 18 month history of intermittent back pain. CT revealed T5 osteolytic lesion with epidural and paravertebral extension. The first CT guided biopsy yielded little information. Histopathological diagnosis of the second biopsy was VH. Vertebroplasty, posterior decompression and fixation were performed followed by postoperative radiotherapy. Her symptoms were resolved immediately after the operation. At 12 months follow-up, no recurrence was detected by CT with contrast enhancement. Surgical decompression, vertebroplasty and fixation are safe and effective for aggressive VH. More attention is needed in determining the algorithm for the diagnosis and treatment of aggressive VH.

Low Incubation Temperature Induces DNA Hypomethylation in Lizard Brains.

PubMed

Paredes, Ursula; Radersma, Reinder; Cannell, Naomi; While, Geoffrey M; Uller, Tobias

2016-07-01

Developmental stress can have organizational effects on suites of physiological, morphological, and behavioral characteristics. In lizards, incubation temperature is perhaps the most significant environmental variable affecting embryonic development. Wall lizards (Podarcis muralis) recently introduced by humans from Italy to England experience stressfully cool incubation conditions, which we here show reduce growth and increase the incidence of scale malformations. Using a methylation-sensitive AFLP protocol optimized for vertebrates, we demonstrate that this low incubation temperature also causes hypomethylation of DNA in brain tissue. A consistent pattern across methylation-susceptible AFLP loci suggests that hypomethylation is a general response and not limited to certain CpG sites. The functional consequences of hypomethylation are unknown, but it could contribute to genome stability and regulation of gene expression. Further studies of the effects of incubation temperature on DNA methylation in ectotherm vertebrates may reveal mechanisms that explain why the embryonic thermal environment often has physiological and behavioral consequences for offspring. © 2016 Wiley Periodicals, Inc.

Collagen type XI alpha1 may be involved in the structural plasticity of the vertebral column in Atlantic salmon (Salmo salar L.).

PubMed

Wargelius, A; Fjelldal, P G; Nordgarden, U; Grini, A; Krossøy, C; Grotmol, S; Totland, G K; Hansen, T

2010-04-01

Atlantic salmon (Salmo salar L.) vertebral bone displays plasticity in structure, osteoid secretion and mineralization in response to photoperiod. Other properties of the vertebral bone, such as mineral content and mechanical strength, are also associated with common malformations in farmed Atlantic salmon. The biological mechanisms that underlie these changes in bone physiology are unknown, and in order to elucidate which factors might be involved in this process, microarray assays were performed on vertebral bone of Atlantic salmon reared under natural or continuous light. Eight genes were upregulated in response to continuous light treatment, whereas only one of them was upregulated in a duplicate experiment. The transcriptionally regulated gene was predicted to code for collagen type XI alpha1, a protein known to be involved in controlling the diameter of fibrillar collagens in mammals. Furthermore, the gene was highly expressed in the vertebrae, where spatial expression was found in trabecular and compact bone osteoblasts and in the chordoblasts of the notochordal sheath. When we measured the expression level of the gene in the tissue compartments of the vertebrae, the collagen turned out to be 150 and 25 times more highly expressed in the notochord and compact bone respectively, relative to the expression in the trabecular bone. Gene expression was induced in response to continuous light, and reduced in compressed vertebrae. The downregulation in compressed vertebrae was due to reduced expression in the compact bone, while expression in the trabecular bone and the notochord was unaffected. These data support the hypothesis that this gene codes for a presumptive collagen type XI alpha1, which may be involved in the regulatory pathway leading to structural adaptation of the vertebral architecture.

Spatial complexity of carcass location influences vertebrate scavenger efficiency and species composition.

PubMed

Smith, Joshua B; Laatsch, Lauren J; Beasley, James C

2017-08-31

Scavenging plays an important role in shaping communities through inter- and intra-specific interactions. Although vertebrate scavenger efficiency and species composition is likely influenced by the spatial complexity of environments, heterogeneity in carrion distribution has largely been disregarded in scavenging studies. We tested this hypothesis by experimentally placing juvenile bird carcasses on the ground and in nests in trees to simulate scenarios of nestling bird carrion availability. We used cameras to record scavengers removing carcasses and elapsed time to removal. Carrion placed on the ground was scavenged by a greater diversity of vertebrates and at > 2 times the rate of arboreal carcasses, suggesting arboreal carrion may represent an important resource to invertebrate scavengers, particularly in landscapes with efficient vertebrate scavenging communities. Nonetheless, six vertebrate species scavenged arboreal carcasses. Rat snakes (Elaphe obsolete), which exclusively scavenged from trees, and turkey vultures (Cathartes aura) were the primary scavengers of arboreal carrion, suggesting such resources are potentially an important pathway of nutrient acquisition for some volant and scansorial vertebrates. Our results highlight the intricacy of carrion-derived food web linkages, and how consideration of spatial complexity in carcass distribution (i.e., arboreal) may reveal important pathways of nutrient acquisition by invertebrate and vertebrate scavenging guilds.

Intraosseous venous malformation of the zygomatico-orbital complex. Case report and literature review with focus on confusions in vascular lesion terms.

PubMed

Fábián, Zoltán; Szabó, György; Petrovan, Cecilia; Horváth, Karin Ursula; Babicsák, Botond; Hüttl, Kálmán; Németh, Zsolt; Bogdán, Sándor

2018-06-01

Intraosseous vascular malformations (VascM) of the facial skeleton are rare entities, raising difficulties even today in their treatment. We present a case for zygomatic intraosseous venous malformation of traumatic etiology with growth dynamics presentation and a multidisciplinary treatment approach, with intravascular embolization surgical ablation and primary reconstructruction using a titanium patient-specific implant (PSI), and a review of the literature for intraosseous vascular lesions of the facial skeleton focusing on the diagnostic syntagms used by the involved medical personnel, to shed light on the confusions over these terms.

[Cor triatriatum. Anatomical forms and surgical treatment of 6 consecutive cases].

PubMed

Bloch, G; Heurtematte, Y; Menu, P; Mesnildrey, P; Casasoprana, A; Magnier, S; Tamari, W; Seurat, M C; Aubry, P; Vernant, P

1988-01-01

Six cases of cor triatriatum documented and operated on at Henri-Mondor hospital between 1980 and 1984 are reported. Ages at the time of surgery ranged from 8 months to 57 years. Four of the 6 patients presented with pulmonary hypertension. Anatomic types consisted of 4 diaphragmatic types and 2 more complex malformations. Associated lesions were present in all but one patients. They consisted mostly of interatrial defects (depending on their position with regard to the intra-atrial membrane, they play a determinant role in the symptomatology) and of a left superior vena cava (which might play a role in the embryogenesis of the malformation). Except for one early postoperative death, results of surgery were excellent for all patients, with a mean follow-up of 5 years. This series, compared with the literature, allows precising the embryologic and anatomic aspects of the malformation and the surgical techniques in complex types.

The nematode homologue of Mediator complex subunit 28, F28F8.5, is a critical regulator of C. elegans development

PubMed Central

Kostrouchová, Markéta; Kostrouch, David; Kaššák, Filip; Kostrouchová, Veronika; Benda, Aleš; Krause, Michael W.; Saudek, Vladimír; Kostrouchová, Marta

2017-01-01

The evolutionarily conserved Mediator complex is a critical player in regulating transcription. Comprised of approximately two dozen proteins, the Mediator integrates diverse regulatory signals through direct protein-protein interactions that, in turn, modulate the influence of Mediator on RNA Polymerase II activity. One Mediator subunit, MED28, is known to interact with cytoplasmic structural proteins, providing a potential direct link between cytoplasmic dynamics and the control of gene transcription. Although identified in many animals and plants, MED28 is not present in yeast; no bona fide MED28 has been described previously in Caenorhabditis elegans. Here, we identify bioinformatically F28F8.5, an uncharacterized predicted protein, as the nematode homologue of MED28. As in other Metazoa, F28F8.5 has dual nuclear and cytoplasmic localization and plays critical roles in the regulation of development. F28F8.5 is a vital gene and its null mutants have severely malformed gonads and do not reproduce. F28F8.5 interacts on the protein level with the Mediator subunits MDT-6 and MDT-30. Our results indicate that F28F8.5 is an orthologue of MED28 and suggest that the potential to link cytoplasmic and nuclear events is conserved between MED28 vertebrate and nematode orthologues. PMID:28603670

Anatomy of the Murine Hepatobiliary System: A Whole-Organ-Level Analysis Using a Transparency Method.

PubMed

Higashiyama, Hiroki; Sumitomo, Hiroyuki; Ozawa, Aisa; Igarashi, Hitomi; Tsunekawa, Naoki; Kurohmaru, Masamichi; Kanai, Yoshiakira

2016-02-01

The biliary tract is a well-branched ductal structure that exhibits great variation in morphology among vertebrates. Its function is maintained by complex constructions of blood vessels, nerves, and smooth muscles, the so-called hepatobiliary system. Although the mouse (Mus musculus) has been used as a model organism for humans, the morphology of its hepatobiliary system has not been well documented at the topographical level, mostly because of its small size and complexity. To reconcile this, we conducted whole-mount anatomical descriptions of the murine extrahepatic biliary tracts with related blood vessels, nerves, and smooth muscles using a recently developed transparentizing method, CUBIC. Several major differences from humans were found in mice: (1) among the biliary arteries, the arteria gastrica sinistra accessoria was commonly found, which rarely appears in humans; (2) the sphincter muscle in the choledochoduodenal junction is unseparated from the duodenal muscle; (3) the pancreatic duct opens to the bile duct without any sphincter muscles because of its distance from the duodenum. This state is identical to a human congenital malformation, an anomalous arrangement of pancreaticobiliary ducts. However, other parts of the murine hepatobiliary system (such as the branching patterns of the biliary tract, blood vessels, and nerves) presented the same patterns as humans and other mammals topologically. Thus, the mouse is useful as an experimental model for studying the human hepatobiliary system. © 2015 Wiley Periodicals, Inc.

The nematode homologue of Mediator complex subunit 28, F28F8.5, is a critical regulator of C. elegans development.

PubMed

Kostrouchová, Markéta; Kostrouch, David; Chughtai, Ahmed A; Kaššák, Filip; Novotný, Jan P; Kostrouchová, Veronika; Benda, Aleš; Krause, Michael W; Saudek, Vladimír; Kostrouchová, Marta; Kostrouch, Zdeněk

2017-01-01

The evolutionarily conserved Mediator complex is a critical player in regulating transcription. Comprised of approximately two dozen proteins, the Mediator integrates diverse regulatory signals through direct protein-protein interactions that, in turn, modulate the influence of Mediator on RNA Polymerase II activity. One Mediator subunit, MED28, is known to interact with cytoplasmic structural proteins, providing a potential direct link between cytoplasmic dynamics and the control of gene transcription. Although identified in many animals and plants, MED28 is not present in yeast; no bona fide MED28 has been described previously in Caenorhabditis elegans. Here, we identify bioinformatically F28F8.5, an uncharacterized predicted protein, as the nematode homologue of MED28. As in other Metazoa, F28F8.5 has dual nuclear and cytoplasmic localization and plays critical roles in the regulation of development. F28F8.5 is a vital gene and its null mutants have severely malformed gonads and do not reproduce. F28F8.5 interacts on the protein level with the Mediator subunits MDT-6 and MDT-30. Our results indicate that F28F8.5 is an orthologue of MED28 and suggest that the potential to link cytoplasmic and nuclear events is conserved between MED28 vertebrate and nematode orthologues.

Evolution of congenital malformations of the umbilical-portal-hepatic venous system.

PubMed

Scalabre, Aurelien; Gorincour, Guillaume; Hery, Geraldine; Gamerre, Marc; Guys, Jean-Michel; de Lagausie, Pascal

2012-08-01

The objective of this study is to describe the evolution of 8 cases of congenital malformations of the umbilical-portal-hepatic venous system diagnosed before the first month of life. All cases of congenital malformation of the portal and hepatic venous system diagnosed prenatally or during the first month of life in our institution were systematically reviewed since November 2000. Clinical features, imaging, and anatomical findings were reviewed, focusing primarily on clinical and radiologic evolution. Eight cases of congenital malformation of the umbilical-portal-hepatic venous system were studied. Fifty percent of these malformations were diagnosed prenatally. We report 4 portosystemic shunts. Three involuted spontaneously, and the fourth one required surgical treatment. We report a variation of the usual anatomy of portal and hepatic veins that remained asymptomatic, an aneurysmal dilatation of a vitelline vein causing portal vein thrombosis that needed prompt surgical treatment with good result, a complex portal and hepatic venous malformation treated operatively, and a persistent right umbilical vein that remained asymptomatic. Prenatal diagnosis of malformations of the umbilical-portal-hepatic venous network is uncommon. Little is known about the postnatal prognosis. Clinical, biologic, and radiologic follow-up by ultrasonography is essential to distinguish pathologic situations from normal anatomical variants. Copyright © 2012 Elsevier Inc. All rights reserved.

A descriptive model for a multidisciplinary unit for colorectal and pelvic malformations.

PubMed

Vilanova-Sanchez, Alejandra; Halleran, Devin R; Reck-Burneo, Carlos A; Gasior, Alessandra C; Weaver, Laura; Fisher, Meghan; Wagner, Andrea; Nash, Onnalisa; Booth, Kristina; Peters, Kaleigh; Williams, Charae; Brown, Sarah Mayer; Lu, Peter; Fuchs, Molly; Diefenbach, Karen; Leonard, Jeffrey R; Hewitt, Geri; McCracken, Kate; Di Lorenzo, Carlo; Wood, Richard J; Levitt, Marc A

2018-04-19

Patients with anorectal malformations (ARM), Hirschsprung disease (HD), and colonic motility disorders often require care from specialists across a variety of fields, including colorectal surgery, urology, gynecology, and GI motility. We sought to describe the process of creating a collaborative process for the care of these complex patients. We developed a model of a devoted center for these conditions that includes physicians, psychologists, social workers, nurses, and advanced practice nurses. Our weekly planning strategy includes a meeting with representatives of all specialties to review all patients prior to evaluation in our multidisciplinary clinic, followed by combined exams under anesthesia or surgical intervention as needed. There are 31 people working directly in the Center at present. From the Center's start in 2014 until 2017, 1258 patients were cared for from all 50 United States and 62 countries. 360 patients had an ARM (110 had a cloacal malformation, 11 had cloacal exstrophy), 223 presented with HD, 71 had a spinal malformation or injury causing neurogenic bowel, 321 had severe functional constipation or colonic dysmotility, and 162 had other diagnoses including familial polyposis, Crohn's disease, or ulcerative colitis. We have had 170 multidisciplinary meetings, 170 multispecialty outpatient, and 52 nurse practitioner clinics. In our bowel management program we have seen a total of 514 patients in 36 sessions. This is the first report describing the design of a multidisciplinary team approach for patients with colorectal and complex pelvic malformations. We found that approaching these patients in a collaborative way allows for combined medical and surgical decisions with many providers simultaneously, facilitates therapy, and can potentially improve patient outcomes. We hope that this model will help establish new-devoted centers in other locations to encourage centralized care for these rare malformations. IV. Copyright © 2018. Published by Elsevier Inc.

Changes in CSF flow after one-stage posterior vertebral column resection in scoliosis patients with syringomyelia and Chiari malformation type I.

PubMed

Wang, Yingsong; Xie, Jingming; Zhao, Zhi; Zhang, Ying; Li, Tao; Si, Yongyu

2013-05-01

Phase contrast-cine MRI (PC-cine MRI) studies in patients with syringomyelia and Chiari malformation Type I (CM-I) have demonstrated abnormal CSF flow across the foramen magnum, which can revert to normal after craniocervical decompression with syrinx shrinkage. In order to investigate the mechanisms leading to postoperative syringomyelia shrinkage, the authors studied the hydrodynamic changes of CSF flow in the craniocervical junction and spinal canal in patients with scoliosis associated with syringomyelia after one-stage deformity correction by posterior vertebral column resection. Preoperative and postoperative CSF flow dynamics at the levels of the foramen magnum, C-7, T-7 (or apex), and L-1 were assessed by electrocardiogram-synchronized cardiac-gated PC-cine MRI in 8 adolescent patients suffering from severe scoliosis with syringomyelia and CM-I (scoliosis group) and undergoing posterior vertebral column resection. An additional 8 patients with syringomyelia and CM-I without spinal deformity (syrinx group) and 8 healthy volunteers (control group) were also enrolled. Mean values were obtained for the following parameters: the duration of a CSF cycle, the duration of caudad CSF flow (CSF downflow [DF]) and cephalad CSF flow (CSF upflow [UF]), the ratio of DF duration to CSF cycle duration (DF%), and the ratio of UF duration to CSF cycle duration (UF%). The ratio of the stationary phase (SP) duration to CSF cycle duration was calculated (SP%). The maximum downflow velocities (VD max) and maximum upflow velocities (VU max) were measured. SPSS (version 14.0) was used for all statistical analysis. Patients in the scoliosis group underwent one-stage posterior vertebral column resection for deformity correction without suboccipital decompression. The mean preoperative coronal Cobb angle was 102.4° (range 76°-138°). The mean postoperative Cobb angle was 41.7° (range 12°-75°), with an average correction rate of 59.3%. During the follow-up, 1 patient with hypermyotonia experienced a significant decrease of muscle tension and 1 patient with reduced anal sphincter tone manifested recovery. A total of 5 patients demonstrated a significant decrease (> 30%) in syrinx size. With respect to changes in CSF flow dynamics, the syrinx group was characterized by slower and shorter downflow than the control group, and the difference was more significant at the foramen magnum and C-7 levels. In patients with scoliosis, CSF downflow at the foramen magnum level was significantly restricted, and a prolonged stationary phase indicated increased obstruction of CSF flow. After posterior vertebral column resection, the peak velocity of CSF flow at the foramen magnum increased, and the downflow phase duration was markedly prolonged. The parameters showed a return to almost normal CSF dynamics at the craniocervical region, and this improvement was maintained for 6-12 months of follow-up. There were distinct abnormalities of CSF flow at the craniocervical junction in patients with syringomyelia. Abnormal dynamics of downflow could be aggravated by associated severe spinal deformity and improved by correction via posterior vertebral column resection.

Schmallenberg virus, a novel orthobunyavirus infection in ruminants in Europe: potential global impact and preventive measures.

PubMed

Conraths, F J; Peters, M; Beer, M

2013-03-01

In autumn 2011, Schmallenberg virus was the first orthobunyavirus detected in Europe. The virus belongs to the Simbu serogroup. Like other orthobunyaviruses, it is apparently transmitted by arthropod vectors, primarily by biting midges (Culicoides spp.). Ruminants and new-world camelids (alpacas) are susceptible to infection. Adult animals may develop mild disease, if any. However, transplacental infection can lead to severe congenital malformations such asarthrogryposis, malformation of the vertebral column (kyphosis, lordosis, scoliosis, torticollis) and of the skull (macrocephaly, brachygnathia inferior) as well as variable malformations of the brain (hydranencephaly, porencephaly, cerebellar hypoplasia, hypoplasia of the brain stem) and of the spinal cord in lambs, goat kids and calves. The infection spread rapidly over large parts of North-Western Europe. Belgium, Denmark, Germany, France, Italy, Luxembourg, the Netherlands, Spain and the United Kingdom were affected in the transmission season 2011/2012. The disease has re-emerged, at least in France, Germany and the United Kingdom during the vector-active season in 2012 and recently spread to Austria, Finland, Poland, Switzerland and Sweden. It remains to be seen whether the infection will establish permanently in the affected area. Measures have been proposed by the World Organisation for Animal Health (OIE) to help countries free from Schmallenberg virus to avoid the introduction of the infection without imposing inappropriate trade barriers. The aim of this article is to provide a state-of-the-art review on Schmallenberg virus 1 year after its first detection.

Excess Imidacloprid Exposure Causes the Heart Tube Malformation of Chick Embryos.

PubMed

Gao, Lin-Rui; Li, Shuai; Zhang, Jing; Liang, Chang; Chen, En-Ni; Zhang, Shi-Yao; Chuai, Manli; Bao, Yong-Ping; Wang, Guang; Yang, Xuesong

2016-11-30

As a neonicotinoid pesticide, imidacloprid is widely used to control sucking insects on agricultural planting and fleas on domestic animals. However, the extent to which imidacloprid exposure has an influence on cardiogensis in early embryogenesis is still poorly understood. In vertebrates, the heart is the first organ to be formed. In this study, to address whether imidacloprid exposure affects early heart development, the early chick embryo has been used as an experimental model because of its accessibility at its early developmental stage. The results demonstrate that exposure of the early chick embryo to imidacloprid caused malformation of heart tube. Furthermore, the data reveal that down-regulation of GATA4, NKX2.5, and BMP4 and up-regulation of Wnt3a led to aberrant cardiomyocyte differentiation. In addition, imidacloprid exposure interfered with basement membrane breakdown, E-cadherin/laminin expression, and mesoderm formation during the epithelial-mesenchymal transition (EMT) in gastrula chick embryos. Finally, the DiI-labeled cell migration trajectory indicated that imidacloprid restricted the cell migration of cardiac progenitors to primary heart field in gastrula chick embryos. A similar observation was also obtained from the cell migration assay of scratch wounds in vitro. Additionally, imidacloprid exposure negatively affected the cytoskeleton structure and expression of corresponding adhesion molecules. Taken together, these results reveal that the improper EMT, cardiac progenitor migration, and differentiation are responsible for imidacloprid exposure-induced malformation of heart tube during chick embryo development.

De novo microduplication at 22q11.21 in a patient with VACTERL association.

PubMed

Schramm, Charlotte; Draaken, Markus; Bartels, Enrika; Boemers, Thomas M; Aretz, Stefan; Brockschmidt, Felix F; Nöthen, Markus M; Ludwig, Michael; Reutter, Heiko

2011-01-01

The non-random association of vertebral defects (V), anorectal malformations (A), cardiac defects (C), tracheoesophageal fistula with esophageal atresia (TE), renal malformations (R), and limb defects (L) is termed VACTERL association. The aim of the present study was to identify microaberrations characterized by a loss or gain of genomic material that contribute to VACTERL association at a genome-wide level. Molecular karyotyping was performed in a cohort of 12 patients with anorectal malformations and at least two additional cardinal features of the VACTERL association. A de novo microduplication at chromosomal region 22q11.21 was identified in a patient presenting with three cardinal VACTERL features (V, A, R) and vesicoureteral reflux, penile hypospadias, caudal regression syndrome, and right-sided congenital equinovarus deformity. Chromosomal region 22q11.2 is known for its susceptibility to rearrangements. Associated syndromes include the velo-cardio-facial and DiGeorge deletion syndromes, and the complementary 22q11.2 duplication syndrome. The findings of the present study extend the phenotypic spectrum of the 22q11.2 duplication syndrome, and indicate that it also predisposes to VACTERL association. We discuss the overlap between the phenotypic features of our patient and those reported for other 22q11.2 aberrations, and propose that dosage-sensitive loci for all of these phenotypic features may reside on 22q11.2. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Accessory mammary tissue associated with congenital and hereditary nephrourinary malformations.

PubMed

Urbani, C E; Betti, R

1996-05-01

The association between polythelia (supernumerary nipple) and kidney and urinary tract malformations (KUTM) is controversial. Some authors reported this association in newborns and infants. Case-control studies dealing with adult subjects are not found in the literature. The purpose of this study is to determine the frequency of the association between accessory mammary tissue (AMT) and congenital and hereditary nephrourinary defects in an adult population compared to a control group. The study was performed in 146 white patients (123 men, 23 women) with AMT out of 2645 subjects consecutively referred to us for physical examination. The following investigations were undertaken: ultrasonographic examination of the abdomen and the kidneys, ECG, echocardiogram, roentgenogram of the vertebral column, urinalysis, and other laboratory tests. A sex- and age-matched control group without any evidence of AMT or lateral displacement of the nipples underwent the same examinations. Kidney and urinary tract malformations were detected in 11 patients with AMT (nine men, two women) and in one control. These data indicate a significantly higher frequency of KUTM in the AMT-affected patients compared to controls (7.53% vs. 0.68%, P < 0.001). A broad spectrum of KUTM was discovered in association with AMT: adult dominant polycystic kidney disease, unilateral renal agenesis, cystic renal dysplasia, familial renal cysts, and congenital stenosis of the pyeloureteral joint. Accessory mammary tissue offers an important clue for congenital and hereditary anomalies of the kidneys and urinary collecting systems. Patients with AMT should, therefore, be extensively examined for the presence of occult nephrouropathies.

Low Frequency Vibrations Induce Malformations in Two Aquatic Species in a Frequency-, Waveform-, and Direction-Specific Manner

PubMed Central

Vandenberg, Laura N.; Stevenson, Claire; Levin, Michael

2012-01-01

Environmental toxicants such as industrial wastes, air particulates from machinery and transportation vehicles, and pesticide run-offs, as well as many chemicals, have been widely studied for their effects on human and wildlife populations. Yet other potentially harmful environmental pollutants such as electromagnetic pulses, noise and vibrations have remained incompletely understood. Because developing embryos undergo complex morphological changes that can be affected detrimentally by alterations in physical forces, they may be particularly susceptible to exposure to these types of pollutants. We investigated the effects of low frequency vibrations on early embryonic development of two aquatic species, Xenopus laevis (frogs) and Danio rerio (zebrafish), specifically focusing on the effects of varying frequencies, waveforms, and applied direction. We observed treatment-specific effects on the incidence of neural tube defects, left-right patterning defects and abnormal tail morphogenesis in Xenopus tadpoles. Additionally, we found that low frequency vibrations altered left-right patterning and tail morphogenesis, but did not induce neural tube defects, in zebrafish. The results of this study support the conclusion that low frequency vibrations are toxic to aquatic vertebrates, with detrimental effects observed in two important model species with very different embryonic architectures. PMID:23251546

C1-C2 instability with severe occipital headache in the setting of vertebral artery facet complex erosion.

PubMed

Taher, Fadi; Bokums, Kristaps; Aichmair, Alexander; Hughes, Alexander P

2014-05-01

An exact understanding of patient vertebral artery anatomy is essential to safely place screws at the atlanto-axial level in posterior arthrodesis. We aim to report a case of erosion of the left vertebral artery into the C1-C2 facet complex with resultant rotatory and lateral listhesis presenting with severe occipital headache. This represents a novel etiology for this diagnosis and our report illustrates technical considerations when instrumenting the C1-C2 segment. We report a case of severe occipital headache due to C1-C2 instability with resultant left C2 nerve compression in the setting of erosion of the vertebral artery into the C1-C2 facet complex. A 68-year-old woman presented with a 12-month history of progressively debilitating headache and neck pain with atlanto-axial instability. Computed tomography (CT) angiography demonstrated erosion of the left vertebral artery into the left C1-C2 facet complex. In addition, the tortuous vertebral arteries had eroded into the C2 pedicles, eliminating the possibility for posterior pedicle screw placement. The patient underwent posterior arthrodesis of C1-C2 utilizing bilateral lateral mass fixation into C1 and bilateral trans-laminar fixation into C2 with resolution of all preoperative complaints. This study constitutes the first report of a tortuous vertebral artery causing the partial destruction of a C1-C2 facet complex, as well as instability, with the clinical presentation of severe occipital headache. It hereby presents a novel etiology for both the development of C1-C2 segment instability as well as the development of occipital headache. Careful evaluation of such lesions utilizing CT angiography is important when formulating a surgical plan.

Spatial complexity of carcass location influences vertebrate scavenger efficiency and species composition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Joshua B.; Laatsch, Lauren J.; Beasley, James C.

Scavenging plays an important role in shaping communities through inter- and intra-specific interactions. Although vertebrate scavenger efficiency and species composition is likely influenced by the spatial complexity of environments, heterogeneity in carrion distribution has largely been disregarded in scavenging studies. We tested this hypothesis by experimentally placing juvenile bird carcasses on the ground and in nests in trees to simulate scenarios of nestling bird carrion availability. We used cameras to record scavengers removing carcasses and elapsed time to removal. Carrion placed on the ground was scavenged by a greater diversity of vertebrates and at > 2 times the rate ofmore » arboreal carcasses, suggesting arboreal carrion may represent an important resource to invertebrate scavengers, particularly in landscapes with efficient vertebrate scavenging communities. Nonetheless, six vertebrate species scavenged arboreal carcasses. Rat snakes (Elaphe obsolete), which exclusively scavenged from trees, and turkey vultures (Cathartes aura) were the primary scavengers of arboreal carrion, suggesting such resources are potentially an important pathway of nutrient acquisition for some volant and scansorial vertebrates. Our results highlight the intricacy of carrion-derived food web linkages, and how consideration of spatial complexity in carcass distribution (i.e., arboreal) may reveal important pathways of nutrient acquisition by invertebrate and vertebrate scavenging guilds.« less

Spatial complexity of carcass location influences vertebrate scavenger efficiency and species composition

DOE PAGES

Smith, Joshua B.; Laatsch, Lauren J.; Beasley, James C.

2017-08-31

Scavenging plays an important role in shaping communities through inter- and intra-specific interactions. Although vertebrate scavenger efficiency and species composition is likely influenced by the spatial complexity of environments, heterogeneity in carrion distribution has largely been disregarded in scavenging studies. We tested this hypothesis by experimentally placing juvenile bird carcasses on the ground and in nests in trees to simulate scenarios of nestling bird carrion availability. We used cameras to record scavengers removing carcasses and elapsed time to removal. Carrion placed on the ground was scavenged by a greater diversity of vertebrates and at > 2 times the rate ofmore » arboreal carcasses, suggesting arboreal carrion may represent an important resource to invertebrate scavengers, particularly in landscapes with efficient vertebrate scavenging communities. Nonetheless, six vertebrate species scavenged arboreal carcasses. Rat snakes (Elaphe obsolete), which exclusively scavenged from trees, and turkey vultures (Cathartes aura) were the primary scavengers of arboreal carrion, suggesting such resources are potentially an important pathway of nutrient acquisition for some volant and scansorial vertebrates. Our results highlight the intricacy of carrion-derived food web linkages, and how consideration of spatial complexity in carcass distribution (i.e., arboreal) may reveal important pathways of nutrient acquisition by invertebrate and vertebrate scavenging guilds.« less

Cloaca--Historical aspects and terminology.

PubMed

Peña, Alberto

2016-04-01

This is a summary of the milestones in the history of the treatment of cloacal malformations. It is based in a comprehensive literature review of the subject, from the early times, followed by a description of the evolution of the surgical maneuvers that were created, to be able to deal with the different anatomical variants of this complex congenital malformation. Copyright © 2016 Elsevier Inc. All rights reserved.

[Neonatal tumours and congenital malformations].

PubMed

Berbel Tornero, O; Ortega García, J A; Ferrís i Tortajada, J; García Castell, J; Donat i Colomer, J; Soldin, O P; Fuster Soler, J L

2008-06-01

The association between pediatric cancer and congenital abnormalities is well known but, there is no exclusive data on the neonatal period and the underlying etiopathogenic mechanisms are unknown. First, to analyze the frequency of neonatal tumours associated with congenital abnormalities; and second, to comment on the likely etiopathogenic hypotheses of a relationship between neonatal tumours and congenital abnormalities. Historical series of neonatal tumours from La Fe University Children's Hospital in Valencia (Spain), from January 1990 to December 1999. Histological varieties of neonatal tumours and associated congenital abnormalities were described. A systematic review of the last 25 years was carried out using Medline, Cancerlit, Index Citation Science and Embase. The search profile used was the combination of "neonatal/congenital-tumors/cancer/neoplasms" and "congenital malformations/birth defects". 72 neonatal tumours were identified (2.8% of all pediatric cancers diagnosed in our hospital) and in 15 cases (20.8%) there was some associated malformation, disease or syndrome. The association between congenital abnormalities and neonatal tumours were: a) angiomas in three patients: two patients with congenital heart disease with a choanal stenosis, laryngomalacia; b) neuroblastomas in two patients: horseshoe kidney with vertebral anomalies and other with congenital heart disease; c) teratomas in two patients: one with cleft palate with vertebral anomalies and other with metatarsal varus; d) one tumour of the central nervous system with Bochdaleck hernia; e) heart tumours in four patients with tuberous sclerosis; f) acute leukaemia in one patient with Down syndrome and congenital heart disease; g) kidney tumour in one case with triventricular hydrocephaly, and h) adrenocortical tumour: hemihypertrophy. The publications included the tumours diagnosed in different pediatric periods and without unified criteria to classify the congenital abnormalities. Little data exist on the neonatal period and the majority are from medical institutions registers. The prevalence varies from 15 to 31.6%. To explain this association, the hypotheses are based on prenatal exposures (preconceptional and transplacental exposure), to mutagenic and carcinogenic risk factors. Neonatal tumours are more often associated to congenital abnormalities than other pediatric cancers. The inclusion and classification criteria needs to be unified to better understand the association between the neonatal tumours and congenital abnormalities. The environmental history in all neonatal tumours associated to congenital abnormalities, including the constitutional and environmental risk factors, will help to improve our knowledge of the underlying prenatal mechanisms and to an advance in its prevention.

Cervical vertebral stenosis associated with a vertebral arch anomaly in the Basset Hound.

PubMed

De Decker, S; De Risio, L; Lowrie, M; Mauler, D; Beltran, E; Giedja, A; Kenny, P J; Gielen, I; Garosi, L; Volk, H

2012-01-01

To report the clinical presentation, imaging characteristics, treatment results, and histopathological findings of a previously undescribed vertebral malformation in the Basset Hound. Retrospective case series study. Eighteen Basset Hounds presented for evaluation of a suspected cervical spinal cord problem. All dogs underwent computed tomography myelography or magnetic resonance imaging of the cervical region. Thirteen male and 5 female Basset Hounds between 6 months and 10.8 years of age (median: 1.4 years) were studied. Clinical signs varied from cervical hyperesthesia to nonambulatory tetraparesis. Imaging demonstrated a well-defined and smooth hypertrophy of the dorsal lamina and spinous process of ≥ 2 adjacent vertebrae. Although this bony abnormality could decrease the ventrodorsal vertebral canal diameter, dorsal midline spinal cord compression was predominantly caused by ligamentum flavum hypertrophy. The articulation between C4 and C5 was most commonly affected. Three dogs were lost to follow-up, 10 dogs underwent dorsal laminectomy, and medical management was initiated in 5 dogs. Surgery resulted in a good outcome with short hospitalization times (median: 4.5 days) in all dogs, whereas medical management produced more variable results. Histopathology confirmed ligamentum flavum hypertrophy and demonstrated the fibrocartilaginous nature of this anomaly. Dorsal lamina and spinous process hypertrophy leading to ligamentum flavum hypertrophy should be included in the differential diagnosis of Basset Hounds with cervical hyperesthesia or myelopathy. Prognosis after decompressive surgery is favorable. Although a genetic component is suspected, additional studies are needed to determine the specific etiology of this disorder. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Cutis tricolor: a literature review and report of five new cases

PubMed Central

Polizzi, Agata; Schepis, Carmelo; Morano, Massimiliano; Strano, Serena; Belfiore, Giuseppe; Palmucci, Stefano; Foti, Pietro Valerio; Pirrone, Concetta; Roggini, Mario; David, Emanule; Salpietro, Vincenzo; Milone, Pietro

2016-01-01

Background Cutis tricolor is a skin abnormality consisting in a combination of congenital hyper- and hypopigmented skin lesions (in the form of paired macules, patches or streaks) in close proximity to each other in a background of normal skin. It is currently regarded as a twin-spotting (mosaic) phenomenon and today is clear that not all cases of cutis tricolor represent one single entity. This phenomenon has been reported so far either: (I) as an purely cutaneous trait; (II) as a part of a complex malformation phenotype (Ruggieri-Happle syndrome, RHS) including distinct facial features, eye (cataract), skeletal (skull and vertebral defects, and long bones dysplasia), nervous system (corpus callosum, cerebellar and white matter anomalies, cavum vergae and holoprosencephaly) and systemic abnormalities; (III) as a distinct type with multiple, disseminated smaller skin macules (cutis tricolor parvimaculata); and (IV) in association with other skin disturbances [e.g., cutis marmorata telangectasica congenita (phacomatosis achromico-melano-marmorata)] or in the context of other skin (e.g., ataxia-telangiectasia and phacomatosis pigmentovascularis, PPV) or complex malformation phenotypes (e.g., microcephaly and dwarfism). Methods (I) Review of the existing literature; and (II) information on our personal experience (clinical, laboratory and imaging data) on new cases with cutis tricolor seen and followed-up at our institutions during years 2010–2016. Results The existing literature revealed 19 previous studies (35 cases) with pure cutaneous or syndromic cutis tricolor phenomena. Our personal experience included 5 unpublished patients (3 boys; 2 girls; currently aged 2 to 14 years) seen and followed-up at our Institutions in Italy who had: (I) skin manifestations of the cutis tricolor type (N=5); (II) skeletal abnormalities including small skull (n=2), obtuse angle of mandible (n=3), mild to moderate scoliosis (n=3), vertebral defects (n=3), and long bones bowing (n=3); mild psychomotor delay (n=3); epilepsy (n=2); anomalies of the corpus callosum (n=3); and cavum vergae (n =2). Conclusions This study further confirms and expands the overall phenotype of cutis tricolor. By literature review and personal experience we conclude that the skin abnormalities of the cutis tricolor type are stable over time; the skeletal defects are mild to moderate and do not progress or cause relevant orthopaedic complications; the neurological/behavioural phenotype does not progress and the paroxysmal events (when present) tend to decrease over time; there is a typical facial phenotype in some patients (long, elongated face, thick and brushy eyebrows, hypertelorism, deep nasal bridge with large bulbous nose and anteverted nostrils), which characterizes a somewhat distinct syndromic phenotype; some patients may develop early onset cataracts. The allelic dydymotic hypothesis of post-zygotic mutations likely involving the same gene loci could well explain the overall skin, bone, lens and nervous system phenomena of migration of different streaks of clones in the different tissues. PMID:27942472

Embolization of Uterine Arteriovenous Malformations Associated with Cyanotic Congenital Heart Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wijesekera, N. T., E-mail: n.wijesekera@doctors.net.uk; Padley, S. P.; Kazmi, F.

2009-09-15

Uterine arteriovenous malformation (AVM) is a rare cause of vaginal bleeding and miscarriage. We report two cases of uterine AVMs in patients with a history of complex congenital heart disease, an association that has not been previously described. Both patients were treated by selective uterine artery embolization, a minimally invasive therapy that has revolutionized the management of uterine AVMs, thus offering an alternative to conventional hysterectomy.

[Impact on environmental factors on the reproductive system and fetal development].

PubMed

Dulskiene, Virginija; Maroziene, Ligita

2002-01-01

A literature review discusses the effect of selected environmental factors on women reproductive system, fetal development and growth. According to recent reports, 2-3% of newborns have congenital malformations. These malformations are caused by interaction of genetic and environmental factors. Exposure of paternal or maternal organisms to environmental hazards may damage germ cells or interfere fetal development, resulting in malformation of various organ systems. Since environmental hazards exposures are complex, it is difficult to establish the primary effect of single factor. Factors, that are known to increase the risk of congenital malformations, preterm delivery or spontaneous abortion, are classified into five groups--psychological, social, biological, physical and chemical factors. The governments of most counties recognize the effect of hazardous environmental factors on public health as global problem. World Health Organization encourages researches, aimed at evaluation of various environmental factors impact on health of pregnant women and their offsprings.

Evolution of complexity in the zebrafish synapse proteome

PubMed Central

Bayés, Àlex; Collins, Mark O.; Reig-Viader, Rita; Gou, Gemma; Goulding, David; Izquierdo, Abril; Choudhary, Jyoti S.; Emes, Richard D.; Grant, Seth G. N.

2017-01-01

The proteome of human brain synapses is highly complex and is mutated in over 130 diseases. This complexity arose from two whole-genome duplications early in the vertebrate lineage. Zebrafish are used in modelling human diseases; however, its synapse proteome is uncharacterized, and whether the teleost-specific genome duplication (TSGD) influenced complexity is unknown. We report the characterization of the proteomes and ultrastructure of central synapses in zebrafish and analyse the importance of the TSGD. While the TSGD increases overall synapse proteome complexity, the postsynaptic density (PSD) proteome of zebrafish has lower complexity than mammals. A highly conserved set of ∼1,000 proteins is shared across vertebrates. PSD ultrastructural features are also conserved. Lineage-specific proteome differences indicate that vertebrate species evolved distinct synapse types and functions. The data sets are a resource for a wide range of studies and have important implications for the use of zebrafish in modelling human synaptic diseases. PMID:28252024

T-Box Genes in the Kidney and Urinary Tract.

PubMed

Kispert, A

2017-01-01

T-box (Tbx) genes encode an ancient group of transcription factors that play important roles in patterning, specification, proliferation, and differentiation programs in vertebrate organogenesis. This is testified by severe organ malformation syndromes in mice homozygous for engineered null alleles of specific T-box genes and by the large number of human inherited organ-specific diseases that have been linked to mutations in these genes. One of the organ systems that has not been associated with loss of specific T-box gene function in human disease for long is the excretory system. However, this has changed with the finding that mutations in TBX18, a member of a vertebrate-specific subgroup within the Tbx1-subfamily of T-box transcription factor genes, cause congenital anomalies of the kidney and urinary tract, predominantly hydroureter and ureteropelvic junction obstruction. Gene expression analyses, loss-of-function studies, and lineage tracing in the mouse suggest a primary role for this transcription factor in specifying the ureteric mesenchyme in the common anlage of the kidney, the ureter, and the bladder. We review the function of Tbx18 in ureterogenesis and discuss the body of evidence that Tbx18 and other members of the T-box gene family, namely, Tbx1, Tbx2, Tbx3, and Tbx20, play additional roles in development and homeostasis of other components of the excretory system in vertebrates. © 2017 Elsevier Inc. All rights reserved.

[Dandy-Walker complex: a clinicopathologic study of 9 cases].

PubMed

Zhang, Xiao-bo; Gu, Yi-qun; Sun, Xiao-fei; Wang, Ying-nan; Wang, Ai-chun

2013-12-01

To investigate the etiology, pathogenesis, clinicopathologic characteristics, clinical prognosis and treatment of Dandy-Walker syndrome. Nine cases of Dandy-Walker syndrome were included in the study. The autopsy findings and clinical history were evaluated along with review of the literature. The causes, pathogenetic mechanism, pathologic features and prognosis of Dandy-Walker syndrome were analyzed. Among 9 Dandy-Walker syndrome cases, six patients presented with variants of Dandy-Walker complex and 3 cases had classic Dandy-Walker malformation. In addition, 4 patients presented with combined lateral ventricle expansion and multiple malformations were seen in 7 cases. Combined umbilical cord abnormality was noted in 4 patients with variant of Dandy-Walker complex and combined placental abnormality was seen in one classic Dandy-Walker syndrome. Dandy-Walker syndrome is a rare disease. In addition to complex pathogenesis with possible genetic and environmental antigenic etiologies, placental and umbilical cord abnormality may be also related to its development.

Size and cell number of the utricle in kinetotically swimming fish: a parabolic aircraft flight study

NASA Astrophysics Data System (ADS)

Bäuerle, A.; Anken, R. H.; Hilbig, R.; Baumhauer, N.; Rahmann, H.

2004-01-01

Humans taking part in parabolic aircraft flights (PAFs) may suffer from space motion sickness (SMS, a kinetosis). Since it has been repeatedly shown earlier that some fish of a given batch also reveal a kinetotic behavior during PAFs (especially so-called spinning movements and looping responses) and due to the homology of the vestibular apparatus among all vertebrates, fish can be used as model systems to investigate the origin of susceptibility to motion sickness. Therefore, we examined the utricular maculae (they are responsible for the internalization of gravity in teleosteans) of fish swimming kinetotically at microgravity in comparison with animals from the same batch who swam normally. On the histological level, it was found that the total number of both sensory and supporting cells of the utricular maculae did not differ between kinetotic animals as compared to normally swimming fish. Cell density (sensory and supporting cells/100 μm 2), however, was reduced in kinetotic animals ( p < 0.0001), which seemed to be due to malformed epithelial cells (increase in cell size) of the kinetotic specimens. Susceptibility to kinetoses may therefore originate in malformed sensory epithelia.

Eye evolution at high resolution: the neuron as a unit of homology.

PubMed

Erclik, Ted; Hartenstein, Volker; McInnes, Roderick R; Lipshitz, Howard D

2009-08-01

Based on differences in morphology, photoreceptor-type usage and lens composition it has been proposed that complex eyes have evolved independently many times. The remarkable observation that different eye types rely on a conserved network of genes (including Pax6/eyeless) for their formation has led to the revised proposal that disparate complex eye types have evolved from a shared and simpler prototype. Did this ancestral eye already contain the neural circuitry required for image processing? And what were the evolutionary events that led to the formation of complex visual systems, such as those found in vertebrates and insects? The recent identification of unexpected cell-type homologies between neurons in the vertebrate and Drosophila visual systems has led to two proposed models for the evolution of complex visual systems from a simple prototype. The first, as an extension of the finding that the neurons of the vertebrate retina share homologies with both insect (rhabdomeric) and vertebrate (ciliary) photoreceptor cell types, suggests that the vertebrate retina is a composite structure, made up of neurons that have evolved from two spatially separate ancestral photoreceptor populations. The second model, based largely on the conserved role for the Vsx homeobox genes in photoreceptor-target neuron development, suggests that the last common ancestor of vertebrates and flies already possessed a relatively sophisticated visual system that contained a mixture of rhabdomeric and ciliary photoreceptors as well as their first- and second-order target neurons. The vertebrate retina and fly visual system would have subsequently evolved by elaborating on this ancestral neural circuit. Here we present evidence for these two cell-type homology-based models and discuss their implications.

Dandy-Walker malformation: analysis of 38 cases.

PubMed

Pascual-Castroviejo, I; Velez, A; Pascual-Pascual, S I; Roche, M C; Villarejo, F

1991-04-01

Thirty-eight cases of Dandy-Walker malformation (DWM) are presented. A female predominance of 3:1 was found. Thirty-two cases (84%) were diagnosed within the 1st year of life. Of these, 17 cases (44.7%) were diagnosed at birth. Ten (26%) were delivered by cesarean section. Thirteen infants (34%) had a birth weight below 3000 g. Several associated malformations were observed, the most frequent being capillary angioma (6 cases); cardiac malformations, ophthalmic anomalies, agenesis of the corpus callosum, malformed limbs, and occipital meningocele were also seen. These observations indicate that DWM represents a disorder of the midline central nervous system indicative of marked genetic and etiologic heterogeneity with the possibility of showing clinical and pathological alterations intra- and extracranially. Macrocephaly was the most frequent physical finding, appearing in 31 cases (82%). Seventeen (44.7%) patients died, 11 before 6 months of age, 3 between 6 and 12 months, and 3 after 1 year. Postmortem studies were performed in 13 patients. Three cases have been lost to follow-up. Mental retardation (IQ below 70) was found in 11 cases (58% of survivors), low intellect (IQ between 70 and 85) in 4, and only 2 patients showed normal intellectual development (IQ more than 85). The high incidence of malformations having several genetic and environmental origins, as well as the high early mortality of patients with DWM, indicate the complexity of this syndrome, which involves the midline developmental field structures. It is not an isolated malformation of the posterior fossa in most cases.

[Aicardi syndrome with Dandy-Walker type malformation].

PubMed

Laguado-Herrera, Yuly V; Manrique-Hernández, Edgar F; Peñaloza-Mantilla, Camilo A; Quintero-Gómez, David A; Contreras-García, Gustavo A; Sandoval-Martínez, Diana K

2015-07-16

Aicardi syndrome (OMIM 304050) was first described in 1965. Its classic triad consists of infantile spasms, partial or total agenesis of the corpus callosum and ocular disorders, such as chorioretinal lacunae. It has been posited that it is due to a mechanism involving X-linked dominant inheritance. We report the case of a full-term female, with no pathological familial history or parental consanguinity, with a prenatal diagnosis of Dandy-Walker type malformation, who presented convulsions, coloboma of the optic nerve, thoracic vertebral block with presence of scoliosis, transfontanellar ultrasound imaging showing agenesis of the corpus callosum and karyotype 46,XX. She was diagnosed with Aicardi syndrome and died at the age of one and a half months. The autopsy revealed supratentorial hydrocephalus with the presence of choroid plexus papilloma, a cyst in the posterior fossa (fourth ventricle), hypoplasia of the cerebellar vermis, agenesis of the left hemisphere of the corpus callosum and cerebellum, characteristic facial features of the syndrome, ogival palate, pectus excavatum, scoliosis, paraovarian cyst and hepatomegaly. Few cases of an association between the pathology and the presence of Dandy-Walker malformation have been described. We report a new case of the association, bearing in mind that the related disorders, mainly agenesis or hypoplasia of the corpus callosum, suggest the existence of an underlying genetic component. A study of the search for the aetiology must be focused on evaluating those genes that are related with neurodevelopment and its activation in the organogenesis stage. The definitive diagnosis establishes the prognosis, management and genetic counselling of the family.

Subtle Decreases in DNA Methylation and Gene Expression at the Mouse Igf2 Locus Following Prenatal Alcohol Exposure: Effects of a Methyl-Supplemented Diet

PubMed Central

Downing, Chris; Johnson, Thomas E; Larson, Colin; Leakey, Tatiana I; Siegfried, Rachel N; Rafferty, Tonya M; Cooney, Craig A

2010-01-01

C57BL/6J (B6) mice are susceptible to in utero growth retardation and a number of morphological malformations following prenatal alcohol exposure, while DBA/2J (D2) mice are relatively resistant. We have previously shown that genomic imprinting may play a role in differential sensitivity between B6 and D2 (Downing and Gilliam 1999). The best characterized mechanism mediating genomic imprinting is differential DNA methylation. In the present study we examined DNA methylation and gene expression, in both embryonic and placental tissue, at the mouse Igf2 locus following in utero ethanol exposure. We also examined the effects of a methyl-supplemented diet on methylation and ethanol teratogenesis. In embryos from susceptible B6 mice, we found small decreases in DNA methylation at four CpG sites in one of the differentially methylated regions of the Igf2 locus; only one of the four sites showed a statistically significant decrease. We observed no significant decreases in methylation in placentae. All Igf2 transcripts showed approximately 1.5 fold decreases following intrauterine alcohol exposure. Placing dams on a methyl-supplemented diet before pregnancy and throughout gestation brought methylation back up to control levels. Methyl-supplementation also resulted in lower prenatal mortality, greater prenatal growth, and decreased digit malformations; it dramatically reduced vertebral malformations. Thus, while prenatal alcohol had only small effects on DNA methylation at the Igf2 locus, placing dams on a methyl-supplemented diet partially ameliorated ethanol teratogenesis. PMID:20705422

[A case of neurofibromatosis type I associated with basal meningocele and abnormal vessels].

PubMed

Yoshioka, H; Sakoda, K; Kohno, H; Hada, H; Hanaya, R; Arita, K; Kurisu, K

1998-03-01

A 21-year-old man with neurofibromatosis type 1 (NF 1) had many widespread cutaneous neurofibroma on his right face. Magnetic resonance imaging (MRI) revealed basal meningocele due to dysplasia of the skull base. Carotid and vertebral angiograms revealed occlusion of the right internal carotid artery, persistent primitive trigeminal artery. We have reviewed the clinical and radiographic features of this case of neurofibromatosis, meningocele and cerebral arterial abnormalities. NF associated with both intracranial vascular malformation and meningocele is very rare, and in our case both were thought to arise congenitally as a manifestation of mesodermal dysplasia. Careful follow up using MRI and MR angiography should be performed for such patients.

A short history of nearly every sense - The evolutionary history of vertebrate sensory cell types.

PubMed

Schlosser, Gerhard

2018-05-08

Evolving from filter feeding chordate ancestors, vertebrates adopted a more active life style. These ecological and behavioral changes went along with an elaboration of the vertebrate head including novel complex paired sense organs such as the eyes, inner ears and olfactory epithelia. However, the photoreceptors, mechanoreceptors and chemoreceptors used in these sense organs have a long evolutionary history and homologous cell types can be recognized in many other bilaterians or even cnidarians. After briefly introducing some of the major sensory cell types found in vertebrates, this review summarizes the phylogenetic distribution of sensory cell types in metazoans and presents a scenario for the evolutionary history of various sensory cell types involving several cell type diversification and fusion events. It is proposed that the evolution of novel cranial sense organs in vertebrates involved the redeployment of evolutionarily ancient sensory cell types for building larger and more complex sense organs.

Assembly and function of the major histocompatibility complex (MHC) I peptide-loading complex are conserved across higher vertebrates.

PubMed

Hinz, Andreas; Jedamzick, Johanna; Herbring, Valentina; Fischbach, Hanna; Hartmann, Jessica; Parcej, David; Koch, Joachim; Tampé, Robert

2014-11-28

Antigen presentation to cytotoxic T lymphocytes via major histocompatibility complex class I (MHC I) molecules depends on the heterodimeric transporter associated with antigen processing (TAP). For efficient antigen supply to MHC I molecules in the ER, TAP assembles a macromolecular peptide-loading complex (PLC) by recruiting tapasin. In evolution, TAP appeared together with effector cells of adaptive immunity at the transition from jawless to jawed vertebrates and diversified further within the jawed vertebrates. Here, we compared TAP function and interaction with tapasin of a range of species within two classes of jawed vertebrates. We found that avian and mammalian TAP1 and TAP2 form heterodimeric complexes across taxa. Moreover, the extra N-terminal domain TMD0 of mammalian TAP1 and TAP2 as well as avian TAP2 recruits tapasin. Strikingly, however, only TAP1 and TAP2 from the same taxon can form a functional heterodimeric translocation complex. These data demonstrate that the dimerization interface between TAP1 and TAP2 and the tapasin docking sites for PLC assembly are conserved in evolution, whereas elements of antigen translocation diverged later in evolution and are thus taxon specific. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Aberrant ligand-induced activation of G protein-coupled estrogen receptor 1 (GPER) results in developmental malformations during vertebrate embryogenesis.

PubMed

Jayasinghe, B Sumith; Volz, David C

2012-01-01

G protein-coupled estrogen receptor 1 (GPER) is a G protein-coupled receptor (GPCR) unrelated to nuclear estrogen receptors but strongly activated by 17β-estradiol in both mammals and fish. To date, the distribution and functional characterization of GPER within reproductive and nonreproductive vertebrate organs have been restricted to juvenile and adult animals. In contrast, virtually nothing is known about the spatiotemporal distribution and function of GPER during vertebrate embryogenesis. Using zebrafish as an animal model, we investigated the potential functional role and expression of GPER during embryogenesis. Based on real-time PCR and whole-mount in situ hybridization, gper was expressed as early as 1 h postfertilization (hpf) and exhibited strong stage-dependent expression patterns during embryogenesis. At 26 and 38 hpf, gper mRNA was broadly distributed throughout the body, whereas from 50 to 98 hpf, gper expression was increasingly localized to the heart, brain, neuromasts, craniofacial region, and somite boundaries of developing zebrafish. Continuous exposure to a selective GPER agonist (G-1)-but not continuous exposure to a selective GPER antagonist (G-15)-from 5 to 96 hpf, or within three developmental windows ranging from 10 to 72 hpf, resulted in adverse concentration-dependent effects on survival, gross morphology, and somite formation within the trunk of developing zebrafish embryos. Importantly, based on co-exposure studies, G-15 blocked severe G-1-induced developmental toxicity, suggesting that G-1 toxicity is mediated via aberrant activation of GPER. Overall, our findings suggest that xenobiotic-induced GPER activation represents a potentially novel and understudied mechanism of toxicity for environmentally relevant chemicals that affect vertebrate embryogenesis.

Spontaneous obliteration of spontaneous vertebral arteriovenous fistula associated with fibromuscular dysplasia after partial surgery: A case report.

PubMed

Iampreechakul, Prasert; Siriwimonmas, Somkiet

2016-12-01

We describe a patient with spontaneous obliteration of spontaneous vertebral arteriovenous fistula (VAVF) associated with fibromuscular dysplasia (FMD) after partial surgery. A 52-year-old hypertensive female woke up one morning with left shoulder pain and weakness of the left upper extremity. A few days later, she developed left-sided audible bruit. She was treated for left frozen shoulder and supportive treatment for audible bruit for four years. She was referred from her general physician to a neurosurgeon because of left arm weakness. Physical examination showed signs of cervical radiculomyelopathy. Magnetic resonance imaging (MRI) showed an extradural mass on the left side of the cervical spinal canal from level C2 to C6. Provisional diagnosis was epidural vascular tumour. Laminectomy and partial removal of the mass was performed at level C5 to C6. Pathological report revealed suspected vascular malformation. Postoperative MRI showed thrombosed epidural vascular structure. Angiography showed dysplastic changes of both vertebral arteries representing FMD with VAVF of the left vertebral artery at level C1-C2. Two years after surgery, follow-up MRI demonstrated complete spontaneous resolution of the large thrombosed epidural vein. Disappearance of her audible bruit immediately after surgery and gradual improvement of her cervical radiculomyelopathy were observed after two years of clinical follow-up. From the literature, we found another 11 patients with 12 VAVFs who had spontaneous obliteration or cure of their fistulas. In the present case, spontaneous obliteration of the fistula seems to correlate with surgery inducing closure of the epidural venous exit leading to thrombosis of the enlarged epidural draining vein. © The Author(s) 2016.

Evolution of vertebrate mechanosensory hair cells and inner ears: toward identifying stimuli that select mutation driven altered morphologies

PubMed Central

Fritzsch, Bernd; Straka, Hans

2014-01-01

Among the major distance senses of vertebrates, the ear is unique in its complex morphological changes during evolution. Conceivably, these changes enable the ear to adapt toward sensing various physically well-characterized stimuli. This review develops a scenario that integrates sensory cell with organ evolution. We propose that molecular and cellular evolution of the vertebrate hair cells occurred prior to the formation of the vertebrate ear. We previously proposed that the genes driving hair cell differentiation, were aggregated in the otic region through developmental re-patterning that generated a unique vertebrate embryonic structure, the otic placode. In agreement with the presence of graviceptive receptors in many vertebrate outgroups, it is likely that the vertebrate ear originally functioned as a simple gravity-sensing organ. Based on the rare occurrence of angular acceleration receptors in vertebrate outgroups, we further propose that the canal system evolved with a more sophisticated ear morphogenesis. This evolving morphogenesis obviously turned the initial otocyst into a complex set of canals and recesses, harboring multiple sensory epithelia each adapted to the acquisition of a specific aspect of a given physical stimulus. As support for this evolutionary progression, we provide several details of the molecular basis of ear development. PMID:24281353

Impact of gene gains, losses and duplication modes on the origin and diversification of vertebrates.

PubMed

Cañestro, Cristian; Albalat, Ricard; Irimia, Manuel; Garcia-Fernàndez, Jordi

2013-02-01

The study of the evolutionary origin of vertebrates has been linked to the study of genome duplications since Susumo Ohno suggested that the successful diversification of vertebrate innovations was facilitated by two rounds of whole-genome duplication (2R-WGD) in the stem vertebrate. Since then, studies on the functional evolution of many genes duplicated in the vertebrate lineage have provided the grounds to support experimentally this link. This article reviews cases of gene duplications derived either from the 2R-WGD or from local gene duplication events in vertebrates, analyzing their impact on the evolution of developmental innovations. We analyze how gene regulatory networks can be rewired by the activity of transposable elements after genome duplications, discuss how different mechanisms of duplication might affect the fate of duplicated genes, and how the loss of gene duplicates might influence the fate of surviving paralogs. We also discuss the evolutionary relationships between gene duplication and alternative splicing, in particular in the vertebrate lineage. Finally, we discuss the role that the 2R-WGD might have played in the evolution of vertebrate developmental gene networks, paying special attention to those related to vertebrate key features such as neural crest cells, placodes, and the complex tripartite brain. In this context, we argue that current evidences points that the 2R-WGD may not be linked to the origin of vertebrate innovations, but to their subsequent diversification in a broad variety of complex structures and functions that facilitated the successful transition from peaceful filter-feeding non-vertebrate ancestors to voracious vertebrate predators. Copyright © 2013 Elsevier Ltd. All rights reserved.

Vascular Anomalies (Part I): Classification and Diagnostics of Vascular Anomalies.

PubMed

Sadick, Maliha; Müller-Wille, René; Wildgruber, Moritz; Wohlgemuth, Walter A

2018-06-06

 Vascular anomalies are a diagnostic and therapeutic challenge. They require dedicated interdisciplinary management. Optimal patient care relies on integral medical evaluation and a classification system established by experts in the field, to provide a better understanding of these complex vascular entities.  A dedicated classification system according to the International Society for the Study of Vascular Anomalies (ISSVA) and the German Interdisciplinary Society of Vascular Anomalies (DiGGefA) is presented. The vast spectrum of diagnostic modalities, ranging from ultrasound with color Doppler, conventional X-ray, CT with 4 D imaging and MRI as well as catheter angiography for appropriate assessment is discussed.  Congenital vascular anomalies are comprised of vascular tumors, based on endothelial cell proliferation and vascular malformations with underlying mesenchymal and angiogenetic disorder. Vascular tumors tend to regress with patient's age, vascular malformations increase in size and are subdivided into capillary, venous, lymphatic, arterio-venous and combined malformations, depending on their dominant vasculature. According to their appearance, venous malformations are the most common representative of vascular anomalies (70 %), followed by lymphatic malformations (12 %), arterio-venous malformations (8 %), combined malformation syndromes (6 %) and capillary malformations (4 %).  The aim is to provide an overview of the current classification system and diagnostic characterization of vascular anomalies in order to facilitate interdisciplinary management of vascular anomalies.   · Vascular anomalies are comprised of vascular tumors and vascular malformations, both considered to be rare diseases.. · Appropriate treatment depends on correct classification and diagnosis of vascular anomalies, which is based on established national and international classification systems, recommendations and guidelines.. · In the classification, diagnosis and treatment of congenital vascular anomalies, radiology plays an integral part in patient management.. · Sadick M, Müller-Wille R, Wildgruber M et al. Vascular Anomalies (Part I): Classification and Diagnostics of Vascular Anomalies. Fortschr Röntgenstr 2018; DOI: 10.1055/a-0620-8925. © Georg Thieme Verlag KG Stuttgart · New York.

Defining the molecular pathologies in cloaca malformation: similarities between mouse and human

PubMed Central

Runck, Laura A.; Method, Anna; Bischoff, Andrea; Levitt, Marc; Peña, Alberto; Collins, Margaret H.; Gupta, Anita; Shanmukhappa, Shiva; Wells, James M.; Guasch, Géraldine

2014-01-01

Anorectal malformations are congenital anomalies that form a spectrum of disorders, from the most benign type with excellent functional prognosis, to very complex, such as cloaca malformation in females in which the rectum, vagina and urethra fail to develop separately and instead drain via a single common channel into the perineum. The severity of this phenotype suggests that the defect occurs in the early stages of embryonic development of the organs derived from the cloaca. Owing to the inability to directly investigate human embryonic cloaca development, current research has relied on the use of mouse models of anorectal malformations. However, even studies of mouse embryos lack analysis of the earliest stages of cloaca patterning and morphogenesis. Here we compared human and mouse cloaca development and retrospectively identified that early mis-patterning of the embryonic cloaca might underlie the most severe forms of anorectal malformation in humans. In mouse, we identified that defective sonic hedgehog (Shh) signaling results in early dorsal-ventral epithelial abnormalities prior to the reported defects in septation. This is manifested by the absence of Sox2 and aberrant expression of keratins in the embryonic cloaca of Shh knockout mice. Shh knockout embryos additionally develop a hypervascular stroma, which is defective in BMP signaling. These epithelial and stromal defects persist later, creating an indeterminate epithelium with molecular alterations in the common channel. We then used these animals to perform a broad comparison with patients with mild-to-severe forms of anorectal malformations including cloaca malformation. We found striking parallels with the Shh mouse model, including nearly identical defective molecular identity of the epithelium and surrounding stroma. Our work strongly suggests that early embryonic cloacal epithelial differentiation defects might be the underlying cause of severe forms of anorectal malformations in humans. Moreover, deranged Shh and BMP signaling is correlated with severe anorectal malformations in both mouse and humans. PMID:24524909

Zebrafish zic2 controls formation of periocular neural crest and choroid fissure morphogenesis.

PubMed

Sedykh, Irina; Yoon, Baul; Roberson, Laura; Moskvin, Oleg; Dewey, Colin N; Grinblat, Yevgenya

2017-09-01

The vertebrate retina develops in close proximity to the forebrain and neural crest-derived cartilages of the face and jaw. Coloboma, a congenital eye malformation, is associated with aberrant forebrain development (holoprosencephaly) and with craniofacial defects (frontonasal dysplasia) in humans, suggesting a critical role for cross-lineage interactions during retinal morphogenesis. ZIC2, a zinc-finger transcription factor, is linked to human holoprosencephaly. We have previously used morpholino assays to show zebrafish zic2 functions in the developing forebrain, retina and craniofacial cartilage. We now report that zebrafish with genetic lesions in zebrafish zic2 orthologs, zic2a and zic2b, develop with retinal coloboma and craniofacial anomalies. We demonstrate a requirement for zic2 in restricting pax2a expression and show evidence that zic2 function limits Hh signaling. RNA-seq transcriptome analysis identified an early requirement for zic2 in periocular neural crest as an activator of alx1, a transcription factor with essential roles in craniofacial and ocular morphogenesis in human and zebrafish. Collectively, these data establish zic2 mutant zebrafish as a powerful new genetic model for in-depth dissection of cell interactions and genetic controls during craniofacial complex development. Copyright © 2017 Elsevier Inc. All rights reserved.

Intraoperative computed tomography with an integrated navigation system in stabilization surgery for complex craniovertebral junction malformation.

PubMed

Yu, Xinguang; Li, Lianfeng; Wang, Peng; Yin, Yiheng; Bu, Bo; Zhou, Dingbiao

2014-07-01

This study was designed to report our preliminary experience with stabilization procedures for complex craniovertebral junction malformation (CVJM) using intraoperative computed tomography (iCT) with an integrated neuronavigation system (NNS). To evaluate the workflow, feasibility and clinical outcome of stabilization procedures using iCT image-guided navigation for complex CVJM. The stabilization procedures in CVJM are complex because of the area's intricate geometry and bony structures, its critical relationship to neurovascular structures and the intricate biomechanical issues involved. A sliding gantry 40-slice computed tomography scanner was installed in a preexisting operating room. The images were transferred directly from the scanner to the NNS using an automated registration system. On the basis of the analysis of intraoperative computed tomographic images, 23 cases (11 males, 12 females) with complicated CVJM underwent navigated stabilization procedures to allow more control over screw placement. The age of these patients were 19-52 years (mean: 33.5 y). We performed C1-C2 transarticular screw fixation in 6 patients to produce atlantoaxial arthrodesis with better reliability. Because of a high-riding transverse foramen on at least 1 side of the C2 vertebra and an anomalous vertebral artery position, 7 patients underwent C1 lateral mass and C2 pedicle screw fixation. Ten additional patients were treated with individualized occipitocervical fixation surgery from the hypoplasia of C1 or constraints due to C2 bone structure. In total, 108 screws were inserted into 23 patients using navigational assistance. The screws comprised 20 C1 lateral mass screws, 26 C2, 14 C3, or 4 C4 pedicle screws, 32 occipital screws, and 12 C1-C2 transarticular screws. There were no vascular or neural complications except for pedicle perforations that were detected in 2 (1.9%) patients and were corrected intraoperatively without any persistent nerves or vessel damage. The overall accuracy of the image guidance system was 98.1%. The duration of interruption during the surgical process for the iCT was 8±1.5 minutes. All patients were clinically evaluated using Nurick grade criteria and for neurological deficits 3 months after surgery. Twenty-one patients (91.3%) improved by at least 1 Nurick grade, whereas the grade remained unchanged in 2 (8.7%) patients. Craniovertebral stability and solid bone fusion was achieved in all patients. NNS was found to correlate well with the intraoperative findings, and the recalibration was uneventful in all cases and had an accuracy of 1.8 mm (range, 0.6-2.2 mm). iCT scanning with integrated NNS was found to be both feasible and beneficial in the stabilization procedures for complex CVJM. In this unusual patient population, the technique seemed to be of value for negotiating complex anatomy and for achieving more control over screw placement.

Intralesional copper wire retention and pingyangmycin injection: an effective combinational therapy for complex venous malformation in soft tissue.

PubMed

Yuan, S-M; Hong, Z-J; Jiang, H-Q; Wang, J; Hu, X-B

2014-04-01

Complex venous malformations (VMs) may extensively involve the soft tissue. The treatment remains a challenge till now. Here we introduce a combinational therapy of copper wires and pingyangmycin (bleomycin A5,PYM). Copper wires were retained in VMs by repeated penetration with a straight needle. Subsequently, PYM solution was injected into the lesion. Eight to 10 days later, copper wires were removed. The dressing was changed every day until the puncture pores healed. Magnetic resonance imaging scanning was performed to observe the change of VMs. From January 2001 to December 2011, 56 patients were treated. During the follow-up period, most of the VMs shrunk obviously. The symptoms were relieved or disappeared. The complications included local pain, temporary paraesthesia and moderate fever, which disappeared quickly after the removal of copper wires. This combinational therapy is a safe and effective approach for the complex VMs in soft tissue.

Nup93, a Vertebrate Homologue of Yeast Nic96p, Forms a Complex with a Novel 205-kDa Protein and Is Required for Correct Nuclear Pore Assembly

PubMed Central

Grandi, Paola; Dang, Tam; Pané, Nelly; Shevchenko, Andrej; Mann, Matthias; Forbes, Douglass; Hurt, Ed

1997-01-01

Yeast and vertebrate nuclear pores display significant morphological similarity by electron microscopy, but sequence similarity between the respective proteins has been more difficult to observe. Herein we have identified a vertebrate nucleoporin, Nup93, in both human and Xenopus that has proved to be an evolutionarily related homologue of the yeast nucleoporin Nic96p. Polyclonal antiserum to human Nup93 detects corresponding proteins in human, rat, and Xenopus cells. Immunofluorescence and immunoelectron microscopy localize vertebrate Nup93 at the nuclear basket and at or near the nuclear entry to the gated channel of the pore. Immunoprecipitation from both mammalian and Xenopus cell extracts indicates that a small fraction of Nup93 physically interacts with the nucleoporin p62, just as yeast Nic96p interacts with the yeast p62 homologue. However, a large fraction of vertebrate Nup93 is extracted from pores and is also present in Xenopus egg extracts in complex with a newly discovered 205-kDa protein. Mass spectrometric sequencing of the human 205-kDa protein reveals that this protein is encoded by an open reading frame, KIAAO225, present in the human database. The putative human nucleoporin of 205 kDa has related sequence homologues in Caenorhabditis elegans and Saccharomyces cerevisiae. To analyze the role of the Nup93 complex in the pore, nuclei were assembled that lack the Nup93 complex after immunodepletion of a Xenopus nuclear reconstitution extract. The Nup93-complex–depleted nuclei are clearly defective for correct nuclear pore assembly. From these experiments, we conclude that the vertebrate and yeast pore have significant homology in their functionally important cores and that, with the identification of Nup93 and the 205-kDa protein, we have extended the knowledge of the nearest-neighbor interactions of this core in both yeast and vertebrates. PMID:9348540

The evolutionary origin of the vertebrate body plan: the problem of head segmentation.

PubMed

Onai, Takayuki; Irie, Naoki; Kuratani, Shigeru

2014-01-01

The basic body plan of vertebrates, as typified by the complex head structure, evolved from the last common ancestor approximately 530 Mya. In this review, we present a brief overview of historical discussions to disentangle the various concepts and arguments regarding the evolutionary development of the vertebrate body plan. We then explain the historical transition of the arguments about the vertebrate body plan from merely epistemological comparative morphology to comparative embryology as a scientific treatment on this topic. Finally, we review the current progress of molecular evidence regarding the basic vertebrate body plan, focusing on the link between the basic vertebrate body plan and the evolutionarily conserved developmental stages (phylotypic stages).

Oxidative stress, endocrine disruption, and malformation of Bufo gargarizans embryo exposed to sub-lethal cadmium concentrations.

PubMed

Wu, Chao; Zhang, Yuhui; Chai, Lihong; Wang, Hongyuan

2017-01-01

Thyroid hormone (TH) is critical for vertebrate postembryonic development as well as embryonic development. Chinese toad (Bufo gargarizans) embryos were exposed to different concentrations of cadmium (5, 50, 100, 200 and 500μg Cd L -1 ) for 7days. Malformations were monitored daily, and growth and development of embryos were measured at day 4 and 7, and type 2 and 3 iodothyronine deiodinase (Dio2 and Dio3), thyroid hormone receptors (TRα and TRβ) mRNA levels were also measured to assess disruption of TH synthesis. In addition, superoxide dismutase (SOD), glutathione peroxidase (GPx) and heat shock proteins (HSPs) mRNA expression were examined to evaluate the ability of scavenging ROS. Our results demonstrated a bimodal inhibitory effect of Cd on the embryo growth and development of Bufo gargarizans. Reduced mean stage, total length and weight were observed at 5, 50, 200 and 500, but not at 100μg Cd L -1 . Embryos malformation occurred in all cadmium treatments. Morphological abnormalities of embryos are characterized by axial flexures, abdominal edema, stunted growth and fin flexure. Real-time PCR results show that exposure to cadmium down-regulated TRα and Dio3 mRNA expression and up-regulated Dio2 mRNA level. SOD and GPx mRNA expression was significantly up-regulated after cadmium exposure. We concluded that cadmium could change mRNA expression of TRα, Dio2 and Dio3 leading the inhibition of growth and development of B. gargarizans embryo, which suggests that cadmium might have the endocrine-disrupting effect in embryos. Moreover, the reduced ability of scavenging ROS induced by cadmium might be responsible for the teratogenic effects of cadmium. Copyright © 2016 Elsevier B.V. All rights reserved.

Holoprosencephaly with caudal dysplasia. Pseudo-trisomy 13 or a distinct entity?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hicks, R.P.B.; Aylsworth, A.S.; Timmons, M.C.

1994-09-01

We have studied three chromosomally normal patients with multiple anomalies that include holoprosencephaly and caudal dysplasia. Each has features found in patients with pseudo-trisomy 13, though each lacks malformations common in that syndrome. Patients 1 and 2 did not have polydactyly and patients 2 and 3 had no congenital heart malformation. Patient 1 is also unusual in that he does not have typical holoprosencephalic facies and is alive at age 25 months. We have also identified two other similar patients in the London Dysmorphology Database, each of which had holoprosencephaly, congenital heart malformation, and imperforate anus. Isolated caudal dysplasia andmore » holoprosencephaly are both causally heterogeneous. They have been reported together rarely in patients with several different syndromes including chromosomal abnormalities, monogenic syndromes, teratogenic insults, and syndromes of unknown cause. Over thirty cases of {open_quotes}pseudo-trisomy 13{close_quotes} have now been reported and eight of these have had features of caudal dysplasia. There have been four with imperforate anus or anal stenosis, one with lumbosacral vertebral anomaly, and three others with bilateral renal agenesis or hypoplasia. Based on our patients and this review of other reported and unreported cases, we suggest that caudal dysplasia may be a significant clinical feature of pseudo-trisomy 13. Alternatively, holoprosencephaly and caudal dysplasia with a normal karyotype may represent a similar though distinct entity. Some may have submicroscopic chromosomal deletions. Molecular studies of regions known to be associated with holoprosencephaly are currently in progress on tissue from Patient 1. We hope these observations will stimulate reports of similarly affected patients to allow better definition of pseudo-trisomy 13 and other overlap syndromes.« less

Muscle complex saving posterior sagittal anorectoplasty.

PubMed

Zaiem, Maher; Zaiem, Feras

2017-05-01

Posterior sagittal anorectoplasty (PSARP) published by DeVries and Peña in 1982 had become the preferred surgical technique for the management of anorectal malformations (ARM). The original technique is based upon complete exposure of the anorectal region by means of a median sagittal incision that runs from the sacrum to the anal dimple, cutting through all muscle structures behind the rectum by dividing the levator muscle and the muscle complex. Then, the rectum is located in front of the levator and within the limits of the muscle complex. In this review, we described Muscle Complex Saving-Posterior Sagittal Anorectoplasty (MCS-PSARP), which is a less invasive technique that consists of keeping this funnel-shaped muscle complex completely intact and not divided, and pulling the rectum through this funnel, toward fixing the new anus to the skin. This technique aimed both to respect the lower part of the sphincter mechanism consisting of the muscle complex, and to avoid the disturbance of this important structure by dividing and resuturing it. We presented six cases of male patients who were born with anorectal malformation (ARM) and underwent MCS-PSARP. The surgical technique proved to be feasible to achieve the dissection of the rectal pouch and the division of the rectourethral fistula in all patients, by opening only the upper part of the sphincter mechanism, the levator muscle, and keeping the lower part consisting of intact muscle complex. The early results in our series are encouraging; however, long-term functional outcomes of these patients are awaited. The surgical tips were also discussed. This proposed approach in the management of anorectal malformation cases provides an opportunity to maximize preservation of the existing continence mechanisms. It preserves the muscle complex components of the levator muscle intact, allowing a better function of the continence mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

Fibroblast growth factor signaling in skeletal development and disease

PubMed Central

Ornitz, David M.; Marie, Pierre J.

2015-01-01

Fibroblast growth factor (FGF) signaling pathways are essential regulators of vertebrate skeletal development. FGF signaling regulates development of the limb bud and formation of the mesenchymal condensation and has key roles in regulating chondrogenesis, osteogenesis, and bone and mineral homeostasis. This review updates our review on FGFs in skeletal development published in Genes & Development in 2002, examines progress made on understanding the functions of the FGF signaling pathway during critical stages of skeletogenesis, and explores the mechanisms by which mutations in FGF signaling molecules cause skeletal malformations in humans. Links between FGF signaling pathways and other interacting pathways that are critical for skeletal development and could be exploited to treat genetic diseases and repair bone are also explored. PMID:26220993

Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis

PubMed Central

Matsui, Takaaki; Thitamadee, Siripong; Murata, Tomoko; Kakinuma, Hisaya; Nabetani, Takuji; Hirabayashi, Yoshio; Hirate, Yoshikazu; Okamoto, Hitoshi; Bessho, Yasumasa

2011-01-01

The assembly of progenitor cells is a crucial step for organ formation during vertebrate development. Kupffer's vesicle (KV), a key organ required for the left–right asymmetric body plan in zebrafish, is generated from a cluster of ∼20 dorsal forerunner cells (DFCs). Although several genes are known to be involved in KV formation, how DFC clustering is regulated and how cluster formation then contributes to KV formation remain unclear. Here we show that positive feedback regulation of FGF signaling by Canopy1 (Cnpy1) controls DFC clustering. Cnpy1 positively regulates FGF signals within DFCs, which in turn promote Cadherin1-mediated cell adhesion between adjacent DFCs to sustain cell cluster formation. When this FGF positive feedback loop is disrupted, the DFC cluster fails to form, eventually leading to KV malformation and defects in the establishment of laterality. Our results therefore uncover both a previously unidentified role of FGF signaling during vertebrate organogenesis and a regulatory mechanism underlying cell cluster formation, which is an indispensable step for formation of a functional KV and establishment of the left–right asymmetric body plan. PMID:21628557

Ear abnormalities in patients with oculo-auriculo-vertebral spectrum (Goldenhar syndrome).

PubMed

Rosa, Rafael Fabiano Machado; Silva, Alessandra Pawelec da; Goetze, Thayse Bienert; Bier, Bianca de Almeida; Almeida, Sheila Tamanini de; Paskulin, Giorgio Adriano; Zen, Paulo Ricardo Gazzola

2011-01-01

Oculo-auriculo-vertebral spectrum (OAVS) is a rare condition characterized by the involvement of the first branchial arches. To investigate the ear abnormalities of a sample of patients with OAVS. The sample consisted of 12 patients with OAVS seen at the Clinical Genetics Unit, UFCSPA/CHSCPA. The study included only patients who underwent mastoid computed tomography and with normal karyotype. We performed a review of its clinical features, giving emphasis to the ear findings. Nine patients were male, the ages ranged from 1 day to 17 years. Ear abnormalities were observed in all patients and involved the external (n = 12), middle (n = 10) and inner ear (n = 3). Microtia was the most frequent finding (n = 12). The most common abnormalities of the middle ear were: opacification (n = 2), displacement (n = 2) and malformation of the ossicular chain. Agenesis of the internal auditory canal (n = 2) was the most frequent alteration of the inner ear. Ear abnormalities are variable in patients with OAVS and often there is no correlation between findings in the external, middle and inner ear. The evaluation of these structures is important in the management of individuals with OAVS.

National Characteristics of Lymphatic Malformations in Children: Inpatient Estimates and Trends in the United States, 2000 to 2009.

PubMed

Cheng, Jeffrey; Liu, Beiyu; Farjat, Alfredo E; Routh, Jonathan

2018-04-01

With ever increasing demands to manage finite resources for health care utilization, we performed an investigation to identify inpatient clinical characteristics and trends in children with lymphatic malformations using the Kids' Inpatient Database, years 2000 to 2009, to help identify populations best suited for resource deployment. Subjects included children 18 years and below with International Classification of Diseases (ICD), ninth revision code: 228.1-lymphangioma, any site. In the United States, between 2000 and 2009, inpatient pediatric patients with lymphatic malformations most commonly affected children aged 3 years and younger, urban hospital locations, and the South and West regions. There was no significant change in age of children with lymphatic malformations or the distribution of their age from year to year, P=0.948 and 0.4223, respectively. No significant evidence for seasonal variation or effect on inpatient admission was identified, P=0.7071. A great majority of admissions (>96%) were in urban locations across each year. There was also no significant change in breakdown of admissions by geographic location, P=0.7133. Further investigation may help to elucidate how to improve access to multidisciplinary vascular anomalies teams to optimize care for these children with unique and complex lymphatic malformations.

Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations

PubMed Central

Cid, Elena; Gomez-Dominguez, Daniel; Martin-Lopez, David; Gal, Beatriz; Laurent, François; Ibarz, Jose M.; Francis, Fiona; Menendez de la Prida, Liset

2014-01-01

Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e., the multiple-hit hypothesis). However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM) in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1); including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders. PMID:24782720

Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations.

PubMed

Cid, Elena; Gomez-Dominguez, Daniel; Martin-Lopez, David; Gal, Beatriz; Laurent, François; Ibarz, Jose M; Francis, Fiona; Menendez de la Prida, Liset

2014-01-01

Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e., the multiple-hit hypothesis). However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM) in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1); including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders.

The Only Known Jawed Vertebrate with Four Eyes and the Bauplan of the Pineal Complex.

PubMed

Smith, Krister T; Bhullar, Bhart-Anjan S; Köhler, Gunther; Habersetzer, Jörg

2018-04-02

The pineal and parapineal organs are dorsal outpocketings of the vertebrate diencephalon that play key roles in orientation and in circadian and annual cycles. Lampreys are four eyed in that both the pineal and parapineal form eyelike photosensory structures, but the pineal is the dominant or sole median photosensory structure in most lower vertebrate clades. The pineal complex has been thought to evolve in a single direction by losing photosensory and augmenting secretory function in the transitions from three-eyed lower vertebrates to two-eyed mammals and archosaurs [1-3]. Yet the widely accepted elaboration of the parapineal instead of the pineal as the primary median photosensory organ [4] in Lepidosauria (lizards, snakes, and tuataras) hints at a more complex evolutionary history. Here we present evidence that a fourth eye re-evolved from the pineal organ at least once within vertebrates, specifically in an extinct monitor lizard, Saniwa ensidens, in which pineal and parapineal eyes were present simultaneously. The tandem midline location of these structures confirms in a striking fashion the proposed homology of the parietal eye with the parapineal organ and refutes the classical model of pineal bilaterality. It furthermore raises questions about the evolution and functional interpretation of the median photosensory organ in other tetrapod clades. Copyright © 2018 Elsevier Ltd. All rights reserved.

The SET1 Complex Selects Actively Transcribed Target Genes via Multivalent Interaction with CpG Island Chromatin.

PubMed

Brown, David A; Di Cerbo, Vincenzo; Feldmann, Angelika; Ahn, Jaewoo; Ito, Shinsuke; Blackledge, Neil P; Nakayama, Manabu; McClellan, Michael; Dimitrova, Emilia; Turberfield, Anne H; Long, Hannah K; King, Hamish W; Kriaucionis, Skirmantas; Schermelleh, Lothar; Kutateladze, Tatiana G; Koseki, Haruhiko; Klose, Robert J

2017-09-05

Chromatin modifications and the promoter-associated epigenome are important for the regulation of gene expression. However, the mechanisms by which chromatin-modifying complexes are targeted to the appropriate gene promoters in vertebrates and how they influence gene expression have remained poorly defined. Here, using a combination of live-cell imaging and functional genomics, we discover that the vertebrate SET1 complex is targeted to actively transcribed gene promoters through CFP1, which engages in a form of multivalent chromatin reading that involves recognition of non-methylated DNA and histone H3 lysine 4 trimethylation (H3K4me3). CFP1 defines SET1 complex occupancy on chromatin, and its multivalent interactions are required for the SET1 complex to place H3K4me3. In the absence of CFP1, gene expression is perturbed, suggesting that normal targeting and function of the SET1 complex are central to creating an appropriately functioning vertebrate promoter-associated epigenome. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

[Larsen syndrome: two reports of cases with spinal cord compromise].

PubMed

Martín Fernández-Mayoralas, D; Fernández-Jaén, A; Muñoz-Jareño, N; Calleja-Pérez, B; San Antonio-Arce, V; Martínez-Boniche, H

Larsen syndrome is characterised by untreatable congenital dislocation of multiple body joints, along with marked foot deformities. These patients have a flattened face with a short nose, a broad depressed nasal bridge and a prominent forehead. In this clinical note our aim is to report two cases that coursed with spinal cord compromise. Case 1: an 18-month-old female with congenital dislocation of knees and hips. The patient had a flat face, sunken root of nose, and carp mouth. Magnetic resonance imaging of the spine showed severe cervical kyphosis secondary to malformation and hypoplasia of the cervical vertebral bodies and important compression of the spinal cord. Clinically, there were also signs of upper motor neuron syndrome, which was especially prominent in the lower limbs. Case 2: a 14-year-old male with a characteristic face and dislocation of the head of the radius. The patient presented amyotrophy of the muscles in the right hand and clinical signs of lower motor neuron syndrome due to neuronal damage secondary to spinal malformations. Larsen syndrome is an infrequent osteochondrodysplasia. Alteration of the spine is common and may give rise to spinal cord compression with varying clinical repercussions which require surgical treatment in the early years of the patient's life.

Loss of unc45a precipitates arteriovenous shunting in the aortic arches

PubMed Central

Anderson, Matthew J.; Pham, Van N.; Vogel, Andreas M.; Weinstein, Brant M.; Roman, Beth L.

2008-01-01

Aortic arch malformations are common congenital disorders that are frequently of unknown etiology. To gain insight into the factors that guide branchial aortic arch development, we examined the process by which these vessels assemble in wild type zebrafish embryos and in kurzschlusstr12 (kus tr12) mutants. In wild type embryos, each branchial aortic arch first appears as an island of angioblasts in the lateral pharyngeal mesoderm, then elaborates by angiogenesis to connect to the lateral dorsal aorta and ventral aorta. In kustr12 mutants, angioblast formation and initial sprouting are normal, but aortic arches 5 and 6 fail to form a lumenized connection to the lateral dorsal aorta. Blood enters these blind-ending vessels from the ventral aorta, distending the arteries and precipitating fusion with an adjacent vein. This arteriovenous malformation (AVM), which shunts nearly all blood directly back to the heart, is not genetically programmed, as its formation correlates with blood flow and aortic arch enlargement. By positional cloning, we have identified a nonsense mutation in unc45a in kustr12 mutants. Our results are the first to ascribe a role for Unc45a, a putative myosin chaperone, in vertebrate development, and identify a novel mechanism by which an AVM can form. PMID:18462713

Spina Bifida

PubMed Central

Copp, Andrew J.; Adzick, N. Scott; Chitty, Lyn S.; Fletcher, Jack M.; Holmbeck, Grayson N.; Shaw, Gary M.

2016-01-01

Spina bifida is a birth defect in which the vertebral column is open (bifid), often with spinal cord involvement. Clinically most significant is myelomeningocele (MMC; open spina bifida) in which the spinal neural tube fails to close during embryonic development. The exposed neural tissue degenerates in utero, resulting in neurological deficit that varies with level of the lesion. Occurring in around 1 per 1000 births worldwide, MMC is one of the commonest congenital malformations, yet its causation is largely unknown. The genetic component of MMC is estimated at 60-70% but few genes have yet been identified, despite much information from mouse models. Non-genetic risk factors include reduced folate intake, maternal anticonvulsant therapy, diabetes mellitus and obesity. Primary prevention by peri-conceptional folic acid has been demonstrated in clinical trials, leading to food fortification programmes in many countries. Prenatal diagnosis is by ultrasound enabling termination of pregnancy. Individuals who survive to birth have their lesions closed surgically, with subsequent management of associated defects, including the Chiari II malformation, hydrocephalus, and urological and orthopaedic sequelae. Fetal surgical repair of MMC has been associated with improved early neurological outcome compared with postnatal operation. MMC affects quality of life during childhood, adolescence, and into adulthood, posing a challenge for individuals, families and society as a whole. PMID:27189655

Young children with severe congenital malformations (VACTERL) expressed mixed feelings about their condition and worries about needles and anaesthesia.

PubMed

Kassa, A-M; Engvall, G; Engstrand Lilja, H

2017-10-01

Our knowledge of the perceptions that children with severe congenital malformations have of their health, treatment and how to improve hospital care is limited. This study focused on patients with vertebral defects, anal atresia, cardiac defects, tracheo-oesophageal fistula, renal anomalies and limb abnormalities (VACTERL). We interviewed 10 children aged five to eight years with VACTERL association who were treated in a Swedish tertiary paediatric surgical centre, using a computer-assisted technique called In My Shoes. The interviews were analysed by qualitative content analysis. The children described their awareness of their health history and said they felt proud but different due to their physical dysfunction. They were happy to visit the hospital to meet familiar staff, but expressed negative feelings about missing normal life. They were afraid of needle-related procedures and not wakening up after anaesthesia. Various ways of coping with difficult situations were expressed, and suggestions to improve hospital care were voiced. Careful follow-up of these children by multidisciplinary teams is crucial to optimise their health and functional status. Fear of medical procedures may be reduced by carefully delivered information, listening to the children, providing continuity of care and creating individual care strategies. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Claudin5a is required for proper inflation of Kupffer's vesicle lumen and organ laterality.

PubMed

Kim, Jeong-Gyun; Bae, Sung-Jin; Lee, Hye Shin; Park, Ji-Hyeon; Kim, Kyu-Won

2017-01-01

Left-right asymmetric organ development is critical to establish a proper body plan of vertebrates. In zebrafish, the Kupffer's vesicle (KV) is a fluid-filled sac which controls asymmetric organ development, and a properly inflated KV lumen by means of fluid influx is a prerequisite for the asymmetric signal transmission. However, little is known about the components that support the paracellular tightness between the KV luminal epithelial cells to sustain hydrostatic pressure during KV lumen expansion. Here, we identified that the claudin5a (cldn5a) is highly expressed at the apical surface of KV epithelial cells and tightly seals the KV lumen. Downregulation of cldn5a in zebrafish showed a failure in organ laterality that resulted from malformed KV. In addition, accelerated fluid influx into KV by combined treatment of forskolin and 3-isobutyl-1-methylxanthine failed to expand the partially-formed KV lumen in cldn5a morphants. However, malformed KV lumen and defective heart laterality in cldn5a morphants were significantly rescued by exogenous cldn5a mRNA, suggesting that the tightness between the luminal epithelial cells is important for KV lumen formation. Taken together, these findings suggest that cldn5a is required for KV lumen inflation and left-right asymmetric organ development.

Claudin5a is required for proper inflation of Kupffer's vesicle lumen and organ laterality

PubMed Central

Kim, Jeong-gyun; Bae, Sung-Jin; Lee, Hye Shin; Park, Ji-Hyeon

2017-01-01

Left-right asymmetric organ development is critical to establish a proper body plan of vertebrates. In zebrafish, the Kupffer’s vesicle (KV) is a fluid-filled sac which controls asymmetric organ development, and a properly inflated KV lumen by means of fluid influx is a prerequisite for the asymmetric signal transmission. However, little is known about the components that support the paracellular tightness between the KV luminal epithelial cells to sustain hydrostatic pressure during KV lumen expansion. Here, we identified that the claudin5a (cldn5a) is highly expressed at the apical surface of KV epithelial cells and tightly seals the KV lumen. Downregulation of cldn5a in zebrafish showed a failure in organ laterality that resulted from malformed KV. In addition, accelerated fluid influx into KV by combined treatment of forskolin and 3-isobutyl-1-methylxanthine failed to expand the partially-formed KV lumen in cldn5a morphants. However, malformed KV lumen and defective heart laterality in cldn5a morphants were significantly rescued by exogenous cldn5a mRNA, suggesting that the tightness between the luminal epithelial cells is important for KV lumen formation. Taken together, these findings suggest that cldn5a is required for KV lumen inflation and left-right asymmetric organ development. PMID:28771527

The notochord curvature in medaka (Oryzias latipes) embryos as a response to ultraviolet A irradiation.

PubMed

Sayed, Alaa El-Din Hamid; Mitani, Hiroshi

2016-11-01

In the present work, the destructive effects of ultraviolet A (UVA; 366nm) irradiation on the developmental stages of Japanese medaka (Oryzias latipes) are revealed in terms of hatching success, mortality rate, and morphological malformations (yolk sac edema, body curvature, fin blistering, and dwarfism). Fertilized eggs in stage 4 were exposed to 15, 30, and 60min/day UVA for 3days in replicates. Fish were staged and aged following the stages established by Iwamatsu [1]. We observed and recorded the hatching time and deformed and dead embryos continuously. The hatching time was prolonged and the deformed and dead embryos numbers were increased by UVA dose increase. At stage 40, samples from each group were fixed to investigate their morphology and histopathology. Some morphological malformations were recorded after UVA exposure in both strains. Histopathological changes were represented as different shapes of curvature in notochord with collapse. The degree of collapsation was depended on the dose and time of UVA exposure. Our findings show that exposure to UVA irradiation caused less vertebral column curvature in medaka fry. Moreover, p53-deficient embryos were more tolerant than those of wild-type (Hd-rR) Japanese medaka. This study indicated the dangerous effects of the UVA on medaka. Copyright © 2016 Elsevier B.V. All rights reserved.

Bisphenol A induces otolith malformations during vertebrate embryogenesis

PubMed Central

2011-01-01

Background The plastic monomer and plasticizer bisphenol A (BPA), used for manufacturing polycarbonate plastic and epoxy resins, is produced at over 2.5 million metric tons per year. Concerns have been raised that BPA acts as an endocrine disruptor on both developmental and reproductive processes and a large body of evidence suggests that BPA interferes with estrogen and thyroid hormone signaling. Here, we investigated BPA effects during embryonic development using the zebrafish and Xenopus models. Results We report that BPA exposure leads to severe malformations of the otic vesicle. In zebrafish and in Xenopus embryos, exposure to BPA during the first developmental day resulted in dose-dependent defects in otolith formation. Defects included aggregation, multiplication and occasionally failure to form otoliths. As no effects on otolith development were seen with exposure to micromolar concentrations of thyroid hormone, 17-ß-estradiol or of the estrogen receptor antagonist ICI 182,780 we conclude that the effects of BPA are independent of estrogen receptors or thyroid-hormone receptors. Na+/K+ ATPases are crucial for otolith formation in zebrafish. Pharmacological inhibition of the major Na+/K+ ATPase with ouabain can rescue the BPA-induced otolith phenotype. Conclusions The data suggest that the spectrum of BPA action is wider than previously expected and argue for a systematic survey of the developmental effects of this endocrine disruptor. PMID:21269433

Bisphenol A induces otolith malformations during vertebrate embryogenesis.

PubMed

Gibert, Yann; Sassi-Messai, Sana; Fini, Jean-Baptiste; Bernard, Laure; Zalko, Daniel; Cravedi, Jean-Pierre; Balaguer, Patrick; Andersson-Lendahl, Monika; Demeneix, Barbara; Laudet, Vincent

2011-01-26

The plastic monomer and plasticizer bisphenol A (BPA), used for manufacturing polycarbonate plastic and epoxy resins, is produced at over 2.5 million metric tons per year. Concerns have been raised that BPA acts as an endocrine disruptor on both developmental and reproductive processes and a large body of evidence suggests that BPA interferes with estrogen and thyroid hormone signaling. Here, we investigated BPA effects during embryonic development using the zebrafish and Xenopus models. We report that BPA exposure leads to severe malformations of the otic vesicle. In zebrafish and in Xenopus embryos, exposure to BPA during the first developmental day resulted in dose-dependent defects in otolith formation. Defects included aggregation, multiplication and occasionally failure to form otoliths. As no effects on otolith development were seen with exposure to micromolar concentrations of thyroid hormone, 17-ß-estradiol or of the estrogen receptor antagonist ICI 182,780 we conclude that the effects of BPA are independent of estrogen receptors or thyroid-hormone receptors. Na+/K+ ATPases are crucial for otolith formation in zebrafish. Pharmacological inhibition of the major Na+/K+ ATPase with ouabain can rescue the BPA-induced otolith phenotype. The data suggest that the spectrum of BPA action is wider than previously expected and argue for a systematic survey of the developmental effects of this endocrine disruptor.

High salt-induced excess reactive oxygen species production resulted in heart tube malformation during gastrulation.

PubMed

Gao, Lin-Rui; Wang, Guang; Zhang, Jing; Li, Shuai; Chuai, Manli; Bao, Yongping; Hocher, Berthold; Yang, Xuesong

2018-09-01

An association has been proved between high salt consumption and cardiovascular mortality. In vertebrates, the heart is the first functional organ to be formed. However, it is not clear whether high-salt exposure has an adverse impact on cardiogenesis. Here we report high-salt exposure inhibited basement membrane breakdown by affecting RhoA, thus disturbing the expression of Slug/E-cadherin/N-cadherin/Laminin and interfering with mesoderm formation during the epithelial-mesenchymal transition(EMT). Furthermore, the DiI + cell migration trajectory in vivo and scratch wound assays in vitro indicated that high-salt exposure restricted cell migration of cardiac progenitors, which was caused by the weaker cytoskeleton structure and unaltered corresponding adhesion junctions at HH7. Besides, down-regulation of GATA4/5/6, Nkx2.5, TBX5, and Mef2c and up-regulation of Wnt3a/β-catenin caused aberrant cardiomyocyte differentiation at HH7 and HH10. High-salt exposure also inhibited cell proliferation and promoted apoptosis. Most importantly, our study revealed that excessive reactive oxygen species(ROS)generated by high salt disturbed the expression of cardiac-related genes, detrimentally affecting the above process including EMT, cell migration, differentiation, cell proliferation and apoptosis, which is the major cause of malformation of heart tubes. © 2018 Wiley Periodicals, Inc.

Coexistence of splenic hemangioma and vascular malformation of the vertebrae.

PubMed

Jalaeikhoo, Hasan; Ariana, Mehdi; Kashfi, Seyed Mohammad Hossein; Azimzadeh, Pedram; Narimani, Ahmad; Dadpay, Masoomeh; Keyhani, Manouchehr

2016-02-09

Cavernous hemangioma is an encapsulated mass of dilated, endothelial lined vascular channels filled with slowly flowing blood. Cavernous hemangioma of the spleen is a rare condition with less than 100 reports so far. Hemangioma of the vertebral is a benign vascular legion around one or two vertebrae. These are usually asymptomatic and discovered incidentally. In this study we reported an extreme rare case of splenic hemangioma coexistence with vascular malformation of the vertebrae. To our knowledge this is the first report of coexistence of splenic hemangioma and hemangioma of the vertebra. A 20-year-old iranian male with splenomegaly, abdominal pain, diarrhea and pancytopenia who was first highly suspicious for malignancy referred to our center for evaluation of the diagnostic workup. After full examination we detected a very rare case with a giant, solitary cavernous hemangioma of the spleen and multiple hemangiomas in his vertebrae. Histopathology of the spleen showed a large cavernous hemangioma occupying almost the entire spleen with large areas of infarction necrosis with multiple hemangiomas of the vertebrae. It is extremely rare to have a splenic hemangioma concurrent with vertebra hemangioma and this is clinically very important to consider splenic hemangioma in differential diagnosis of splenomegaly for a better therapeutic management in related patients.

Hypomelanosis of Ito: neurological and psychiatric pictures in developmental age.

PubMed

Parisi, L; Di Filippo, T; Roccella, M

2012-02-01

Hypomelanosis of Ito (HOI) is a multisystem neurocutaneous disorder. In the described cases, cutaneous manifestations (unilateral or bilateral streaks and swirls of hypomelanosis with regular and confluent borders) and extracutaneous abnormalities are often associated. Extracutaneous abnormalities involve the musculoskeletal system (scoliosis, vertebral anomalies, cranial-facial malformations) and other organs, as well as the central nervous system (CNS). The most significant anomalies of the CNS are psychomotor retardation and cognitive deficit. Autism, epilepsy, language disorders, cerebral malformations (neural migration disorders, cerebral hypoplasia, cortical atrophy, agenesis of the corpus callosum) are sometimes present. Numerous abnormal chromosomal patterns have been observed. HOI is usually a sporadic disorder; though autosomal dominant transmission has been suggested, recessive and X-linked inheritance patterns have also been reported. This study describes five children with HOI presenting with various features of the clinical spectrum of the syndrome. Some of these cases were referred for psychomotor therapy as part of an integrated neuropsychologic and psychomotor treatment support program. In this view, psychomotor treatment aims to promote the emotional-relational component, to overcome rigid divisions, and to integrate learning-related cognitive aspects with psychodynamic concepts. Finally, the goals of psychological and social support are to help the parents accept their child's handicap, understand the child's behavior, plan future pregnancies, and foster an environment for their child's integration.

[Mathematical calculation of strength of the vertebral column in surgical treatment of unstable fractures of the spine].

PubMed

Orlov, S V; Kanykin, A Iu; Moskalev, V P; Shchedrenok, V V; Sedov, R L

2009-01-01

A mathematical model of a three-vertebra complex was developed in order to make an exact calculation of loss of supporting ability of the vertebral column in trauma. Mathematical description of the dynamic processes was based on Lagrange differential equation of the second order. The degree of compression and instability of the three-vertebra complex, established using mathematical modeling, determines the decision on the surgical treatment and might be considered as a prognostic criterion of the course of the compression trauma of the spine. The method of mathematical modeling of supporting ability of the vertebral column was used in 72 patients.

Evolution and Development of Ventricular Septation in the Amniote Heart

PubMed Central

Poelmann, Robert E.; Groot, Adriana C. Gittenberger-de; Vicente-Steijn, Rebecca; Wisse, Lambertus J.; Bartelings, Margot M.; Everts, Sonja; Hoppenbrouwers, Tamara; Kruithof, Boudewijn P. T.; Jensen, Bjarke; de Bruin, Paul W.; Hirasawa, Tatsuya; Kuratani, Shigeru; Vonk, Freek; van de Put, Jeanne M. M. S.; de Bakker, Merijn A.; Richardson, Michael K.

2014-01-01

During cardiogenesis the epicardium, covering the surface of the myocardial tube, has been ascribed several functions essential for normal heart development of vertebrates from lampreys to mammals. We investigated a novel function of the epicardium in ventricular development in species with partial and complete septation. These species include reptiles, birds and mammals. Adult turtles, lizards and snakes have a complex ventricle with three cava, partially separated by the horizontal and vertical septa. The crocodilians, birds and mammals with origins some 100 million years apart, however, have a left and right ventricle that are completely separated, being a clear example of convergent evolution. In specific embryonic stages these species show similarities in development, prompting us to investigate the mechanisms underlying epicardial involvement. The primitive ventricle of early embryos becomes septated by folding and fusion of the anterior ventricular wall, trapping epicardium in its core. This folding septum develops as the horizontal septum in reptiles and the anterior part of the interventricular septum in the other taxa. The mechanism of folding is confirmed using DiI tattoos of the ventricular surface. Trapping of epicardium-derived cells is studied by transplanting embryonic quail pro-epicardial organ into chicken hosts. The effect of decreased epicardium involvement is studied in knock-out mice, and pro-epicardium ablated chicken, resulting in diminished and even absent septum formation. Proper folding followed by diminished ventricular fusion may explain the deep interventricular cleft observed in elephants. The vertical septum, although indistinct in most reptiles except in crocodilians and pythonidsis apparently homologous to the inlet septum. Eventually the various septal components merge to form the completely septated heart. In our attempt to discover homologies between the various septum components we aim to elucidate the evolution and development of this part of the vertebrate heart as well as understand the etiology of septal defects in human congenital heart malformations. PMID:25192012

[Pyelonephritis with massive renal tissue necrosis in child with urinary tract malformation--a case report].

PubMed

Pawlak-Bratkowska, Monika; Finke, Daria; Olejniczak, Dariusz; Midel, Anna; Tkaczyk, Marcin

2009-04-01

The aim of the case report is presentation of unusual and heavy clinical course of pyelonephritis with renal tissue necrosis in a child with urinary tract malformation. Nine month old girl was admitted to hospital in heavy clinical status due to pyelonephritis--urosepsis. It was complicated by acute renal insufficiency. Patient was treated by broad-spectrum antibiotics and parenteral nutrition. She was feverish for 14 days. Computed tomography done in order to exclude abdominal abscess showed massive renal tissue necrosis of on both sides. Antibiotic treatment was successful after 6 weeks. Urological evaluation revealed bilateral vesico-ureteral refluxes grade IV. Scintigraphy showed multiple scars. Patient was treated Deflux injections (twice). We noted 5 urinary tract recurrences despite antibiotic profilaxis. GFR of 75 ml/min/1.73 m2 was estimated at age of 16 m. Immunodeficiency or malignancy as background of clinical course were excluded. The case we describe presents severe clinical course of pyelonephritis due to complex urinary tract malformation that is to be considered despite based on modern publications "sparing" strategies of diagnosis and profilaxis in urinary tract malformations.

Vertebrate pheromones and other semiochemicals: the potential for accommodating complexity in signalling by volatile compounds for vertebrate management

PubMed Central

Pickett, John A.; Barasa, Stephen; Birkett, Michael A.

2014-01-01

The interaction between volatile and non-volatile, e.g. proteinaceous, components of pheromone and other semiochemical-based signalling systems presents a daunting set of problems for exploitation in the management of vertebrates, good or bad. Aggravating this is the complexity of the mixtures involved with pheromones, not only by definition associated with each species, but also with individual members of that species and their positions within their immediate communities. Nonetheless, already in some contexts, particularly where signals are perceived at other trophic levels from those of the vertebrates, e.g. by arthropods, reductionist approaches can be applied whereby the integrity of complex volatile mixtures is maintained, but perturbed by augmentation with individual components. In the present article, this is illustrated for cattle husbandry, fish farming and human health. So far, crude formulations have been used to imitate volatile semiochemical interactions with non-volatile components, but new approaches must be developed to accommodate more sophisticated interactions and not least the activities of the non-volatile, particularly proteinaceous components, currently being deduced. PMID:25109967

Diversity of bile salts in fish and amphibians: evolution of a complex biochemical pathway.

PubMed

Hagey, Lee R; Møller, Peter R; Hofmann, Alan F; Krasowski, Matthew D

2010-01-01

Bile salts are the major end metabolites of cholesterol and are also important in lipid and protein digestion, as well as shaping of the gut microflora. Previous studies had demonstrated variation of bile salt structures across vertebrate species. We greatly extend prior surveys of bile salt variation in fish and amphibians, particularly in analysis of the biliary bile salts of Agnatha and Chondrichthyes. While there is significant structural variation of bile salts across all fish orders, bile salt profiles are generally stable within orders of fish and do not correlate with differences in diet. This large data set allowed us to infer evolutionary changes in the bile salt synthetic pathway. The hypothesized ancestral bile salt synthetic pathway, likely exemplified in extant hagfish, is simpler and much shorter than the pathway of most teleost fish and terrestrial vertebrates. Thus, the bile salt synthetic pathway has become longer and more complex throughout vertebrate evolution. Analysis of the evolution of bile salt synthetic pathways provides a rich model system for the molecular evolution of a complex biochemical pathway in vertebrates.

Phylostratigraphic Profiles in Zebrafish Uncover Chordate Origins of the Vertebrate Brain

PubMed Central

Šestak, Martin Sebastijan; Domazet-Lošo, Tomislav

2015-01-01

An elaborated tripartite brain is considered one of the important innovations of vertebrates. Other extant chordate groups have a more basic brain organization. For instance, cephalochordates possess a relatively simple brain possibly homologous to the vertebrate forebrain and hindbrain, whereas tunicates display the tripartite organization, but without the specialized brain centers. The difference in anatomical complexity is even more pronounced if one compares chordates with other deuterostomes that have only a diffuse nerve net or alternatively a rather simple central nervous system. To gain a new perspective on the evolutionary roots of the complex vertebrate brain, we made here a phylostratigraphic analysis of gene expression patterns in the developing zebrafish (Danio rerio). The recovered adaptive landscape revealed three important periods in the evolutionary history of the zebrafish brain. The oldest period corresponds to preadaptive events in the first metazoans and the emergence of the nervous system at the metazoan–eumetazoan transition. The origin of chordates marks the next phase, where we found the overall strongest adaptive imprint in almost all analyzed brain regions. This finding supports the idea that the vertebrate brain evolved independently of the brains within the protostome lineage. Finally, at the origin of vertebrates we detected a pronounced signal coming from the dorsal telencephalon, in agreement with classical theories that consider this part of the cerebrum a genuine vertebrate innovation. Taken together, these results reveal a stepwise adaptive history of the vertebrate brain where most of its extant organization was already present in the chordate ancestor. PMID:25415965

Deletion of a conserved regulatory element required for Hmx1 expression in craniofacial mesenchyme in the dumbo rat: a newly identified cause of congenital ear malformation

PubMed Central

Quina, Lely A.; Kuramoto, Takashi; Luquetti, Daniela V.; Cox, Timothy C.; Serikawa, Tadao; Turner, Eric E.

2012-01-01

SUMMARY Hmx1 is a homeodomain transcription factor expressed in the developing eye, peripheral ganglia, and branchial arches of avian and mammalian embryos. Recent studies have identified a loss-of-function allele at the HMX1 locus as the causative mutation in the oculo-auricular syndrome (OAS) in humans, characterized by ear and eye malformations. The mouse dumbo (dmbo) mutation, with similar effects on ear and eye development, also results from a loss-of-function mutation in the Hmx1 gene. A recessive dmbo mutation causing ear malformation in rats has been mapped to the chromosomal region containing the Hmx1 gene, but the nature of the causative allele is unknown. Here we show that dumbo rats and mice exhibit similar neonatal ear and eye phenotypes. In midgestation embryos, dumbo rats show a specific loss of Hmx1 expression in neural-crest-derived craniofacial mesenchyme (CM), whereas Hmx1 is expressed normally in retinal progenitors, sensory ganglia and in CM, which is derived from mesoderm. High-throughput resequencing of 1 Mb of rat chromosome 14 from dmbo/dmbo rats, encompassing the Hmx1 locus, reveals numerous divergences from the rat genomic reference sequence, but no coding changes in Hmx1. Fine genetic mapping narrows the dmbo critical region to an interval of ∼410 kb immediately downstream of the Hmx1 transcription unit. Further sequence analysis of this region reveals a 5777-bp deletion located ∼80 kb downstream in dmbo/dmbo rats that is not apparent in 137 other rat strains. The dmbo deletion region contains a highly conserved domain of ∼500 bp, which is a candidate distal enhancer and which exhibits a similar relationship to Hmx genes in all vertebrate species for which data are available. We conclude that the rat dumbo phenotype is likely to result from loss of function of an ultraconserved enhancer specifically regulating Hmx1 expression in neural-crest-derived CM. Dysregulation of Hmx1 expression is thus a candidate mechanism for congenital ear malformation, most cases of which remain unexplained. PMID:22736458

Stereotactic radiosurgery for deep intracranial arteriovenous malformations, part 1: Brainstem arteriovenous malformations.

PubMed

Cohen-Inbar, Or; Ding, Dale; Chen, Ching-Jen; Sheehan, Jason P

2016-02-01

The management of brainstem arteriovenous malformations (AVM) are one of the greatest challenges encountered by neurosurgeons. Brainstem AVM have a higher risk of hemorrhage compared to AVM in other locations, and rupture of these lesions commonly results in devastating neurological morbidity and mortality. The potential morbidity associated with currently available treatment modalities further compounds the complexity of decision making for affected patients. Stereotactic radiosurgery (SRS) has an important role in the management of brainstem AVM. SRS offers acceptable obliteration rates with lower risks of hemorrhage occurring during the latency period. Complex nidal architecture requires a multi-disciplinary treatment approach. Nidi partly involving subpial/epipial regions of the dorsal midbrain or cerebellopontine angle should be considered for a combination of endovascular embolization, micro-surgical resection and SRS. Considering the fact that incompletely obliterated lesions (even when reduced in size) could still cause lethal hemorrhages, additional treatment, including repeat SRS and surgical resection should be considered when complete obliteration is not achieved by first SRS. Patients with brainstem AVM require continued clinical and radiological observation and follow-up after SRS, well after angiographic obliteration has been confirmed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mutations in extracellular matrix genes NID1 and LAMC1 cause autosomal dominant Dandy-Walker malformation and occipital cephaloceles

PubMed Central

Darbro, Benjamin W.; Mahajan, Vinit B.; Gakhar, Lokesh; Skeie, Jessica M.; Campbell, Elizabeth; Wu, Shu; Bing, Xinyu; Millen, Kathleen J.; Dobyns, William B.; Kessler, John A.; Jalali, Ali; Cremer, James; Segre, Alberto; Manak, J. Robert; Aldinger, Kimerbly A.; Suzuki, Satoshi; Natsume, Nagato; Ono, Maya; Hai, Huynh Dai; Viet, Le Thi; Loddo, Sara; Valente, Enza M.; Bernardini, Laura; Ghonge, Nitin; Ferguson, Polly J.; Bassuk, Alexander G.

2013-01-01

We performed whole-exome sequencing of a family with autosomal dominant Dandy-Walker malformation and occipital cephaloceles (ADDWOC) and detected a mutation in the extracellular matrix protein encoding gene NID1. In a second family, protein interaction network analysis identified a mutation in LAMC1, which encodes a NID1 binding partner. Structural modeling the NID1-LAMC1 complex demonstrated that each mutation disrupts the interaction. These findings implicate the extracellular matrix in the pathogenesis of Dandy-Walker spectrum disorders. PMID:23674478

Dandy-Walker malformation and neurocutaneous melanosis in a three-month-old infant

PubMed Central

Mahgoub, Shaza Mohamed; Yassin, Rehab Omer; Osman, Atika Mohamed

2013-01-01

Dandy-Walker Malformation (DWM) is a rare congenital malformation of the brain. It is characterized by cystic enlargement of the fourth ventricle which is communicating with an enlarged posterior fossa, cerebellar dysgenesis, high tentorial insertion and hydrocephalus. Neurocutaneous Melanosis (NCM) is a congenital neurocutaneous syndrome characterized by large or multiple melanocytic nevi and benign or malignant melanocytic tumors of the leptomeninges. We report three months old boy who presented with projectile vomiting associated with a noticeable increase in head size. Several congenital nevi were seen all over his body with evident signs of hydrocephalus. The association of DWM and NCM is a rare complex, and to our knowledge, this is the eleventh case to be reported in the literature. In this article, we discuss the proposed pathogenesis, classification and management of the condition. PMID:27493376

The molecular genetics of holoprosencephaly

PubMed Central

Roessler, Erich; Muenke, Maximilian

2009-01-01

Holoprosencephaly (or HPE) has captivated the imagination of Man for millennia because its most extreme manifestation, the single-eyed cyclopic newborn infant, brings to mind the fantastical creature Cyclops from Greek mythology. Attempting to understand this common malformation of the forebrain in modern medical terms requires a systematic synthesis of genetic, cytogenetic and environmental information typical for studies of a complex disorder. However, even with the advances in our understanding of HPE in recent years, there are significant obstacles remaining to fully understand its heterogeneity and extensive variability in phenotype. General lessons learned from HPE will likely be applicable to other malformation syndromes. Here we outline the common, and rare, genetic and environmental influences on this conserved developmental program of forebrain development and illustrate the similarities and differences between these malformations in humans and those of animal models. PMID:20104595

The molecular genetics of holoprosencephaly.

PubMed

Roessler, Erich; Muenke, Maximilian

2010-02-15

Holoprosencephaly (HPE) has captivated the imagination of Man for millennia because its most extreme manifestation, the single-eyed cyclopic newborn infant, brings to mind the fantastical creature Cyclops from Greek mythology. Attempting to understand this common malformation of the forebrain in modern medical terms requires a systematic synthesis of genetic, cytogenetic, and environmental information typical for studies of a complex disorder. However, even with the advances in our understanding of HPE in recent years, there are significant obstacles remaining to fully understand its heterogeneity and extensive variability in phenotype. General lessons learned from HPE will likely be applicable to other malformation syndromes. Here we outline the common, and rare, genetic and environmental influences on this conserved developmental program of forebrain development and illustrate the similarities and differences between these malformations in humans and those of animal models. 2010 Wiley-Liss, Inc.

A new heart for a new head in vertebrate cardiopharyngeal evolution.

PubMed

Diogo, Rui; Kelly, Robert G; Christiaen, Lionel; Levine, Michael; Ziermann, Janine M; Molnar, Julia L; Noden, Drew M; Tzahor, Eldad

2015-04-23

It has been more than 30 years since the publication of the new head hypothesis, which proposed that the vertebrate head is an evolutionary novelty resulting from the emergence of neural crest and cranial placodes. Neural crest generates the skull and associated connective tissues, whereas placodes produce sensory organs. However, neither crest nor placodes produce head muscles, which are a crucial component of the complex vertebrate head. We discuss emerging evidence for a surprising link between the evolution of head muscles and chambered hearts - both systems arise from a common pool of mesoderm progenitor cells within the cardiopharyngeal field of vertebrate embryos. We consider the origin of this field in non-vertebrate chordates and its evolution in vertebrates.

A new heart for a new head in vertebrate cardiopharyngeal evolution

PubMed Central

Diogo, Rui; Kelly, Robert G.; Christiaen, Lionel; Levine, Michael; Ziermann, Janine M.; Molnar, Julia L.; Noden, Drew M.; Tzahor, Eldad

2015-01-01

It has been more than 30 years since the publication of the new head hypothesis, which proposed that the vertebrate head is an evolutionary novelty resulting from the emergence of neural crest and cranial placodes. Neural crest generates the skull and associated connective tissues, whereas placodes produce sensory organs. However, neither crest nor placodes produce head muscles, which are a crucial component of the complex vertebrate head. We discuss emerging evidence for a surprising link between the evolution of head muscles and chambered hearts — both systems arise from a common pool of mesoderm progenitor cells within the cardiopharyngeal field of vertebrate embryos. We consider the origin of this field in non-vertebrate chordates and its evolution in vertebrates. PMID:25903628

Skeletal development and abnormalities of the vertebral column and of the fins in hatchery-reared turbot Scophthalmus maximus.

PubMed

Tong, X H; Liu, Q H; Xu, S H; Ma, D Y; Xiao, Z Z; Xiao, Y S; Li, J

2012-03-01

To describe the skeletal development and abnormalities in turbot Scophthalmus maximus, samples were collected every day from hatching to 60 days after hatching (DAH). A whole-mount cartilage and bone-staining technique was used. Vertebral ontogeny started with the formation of anterior haemal arches at 5·1 mm standard length (L(S) ) c. 11 DAH, and was completed by the full attainment of parapophyses at 16·9 mm L(S) c. 31 DAH. Vertebral centra started to develop at 6·3 mm L(S) c. 16 DAH and ossification in all centra was visible at 11·0 mm L(S) c. 25 DAH. The caudal fin appeared at 5·1 mm L(S) c. 11 DAH and ossification was visible at 20·6 mm L(S) c. 37 DAH. The onset of dorsal and anal fin elements appeared at 5·8 mm L(S) c. 15 DAH and 6·3 mm L(S) c. 16 DAH, respectively. Ossifications of both dorsal fin and anal fin were visible at 20·6 mm L(S) c. 37 DAH. The pectorals were the only fins present before first feeding, their ossifications were completed at 23·5 mm L(S) c. 48 DAH. Pelvic fins began forming at 7·2 mm L(S) c. 19 DAH and calcification of the whole structure was visible at 19·8 mm L(S) c. 36 DAH. In the present study, 24 types of skeletal abnormalities were observed. About 51% of individuals presented skeletal abnormalities, and the highest occurrence was found in the haemal region of the vertebral column. As for each developmental stage, the most common abnormalities were in the dorsal fin during early metamorphic period (stage 2), vertebral fusion during climax metamorphosis (stage 3) and caudal fin abnormality during both late-metamorphic period (stage 4) and post-metamorphic period (stage 5). Such research will be useful for early detection of skeletal malformations during different growth periods of reared S. maximus. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

Trans-sphenoidal encephalocele in association with Dandy-Walker complex and cardiovascular anomalies.

PubMed

Joy, H M; Barker, C S; Small, J H; Armitage, M

2001-01-01

We present a case of trans-sphenoidal encephalomeningocele in association with a posterior cranial fossa malformation which fulfils the criteria for the Dandy-Walker complex [1]. Congenital cardiovascular defects were also present. An abnormality of neural crest development may be responsible for the combined occurrence of these anomalies.

Anatomic variants in Dandy-Walker complex.

PubMed

Jurcă, Maria Claudia; Kozma, Kinga; Petcheşi, CodruŢa Diana; Bembea, Marius; Pop, Ovidiu Laurean; MuŢiu, Gabriela; Coroi, Mihaela Cristiana; Jurcă, Alexandru Daniel; Dobjanschi, Luciana

2017-01-01

Dandy-Walker complex (DWC) is a malformative association of the central nervous system. DWC includes four different types: Dandy-Walker malformation (vermis agenesis or hypoplasia, cystic dilatation of the fourth ventricle and a large posterior fossa); Dandy-Walker variant (vermis hypoplasia, cystic dilatation of the fourth ventricle, normal posterior fossa); mega cysterna magna (large posterior fossa, normal vermis and fourth ventricle) and posterior fossa arachnoid cyst. We present and discuss four cases with different morphological and clinical forms of the Dandy-Walker complex. In all four cases, diagnosis was reached by incorporation of clinical (macrocephaly, seizures) and imaging [X-ray, computed tomography (CT), magnetic resonance imaging (MRI)] data. Two patients were diagnosed with Dandy-Walker complex, one patient was diagnosed with Dandy-Walker variant in a rare association with neurofibromatosis and one patient was diagnosed with a posterior fossa arachnoid cyst associated with left-sided Claude Bernard-Horner syndrome, congenital heart disease (coarctation of the aorta, mitral stenosis) and gastroesophageal reflux. In all forms of DWC, the clinical, radiological and functional manifestations are variable and require adequate diagnostic and therapeutic measures.

[Orbito-palpebral vascular pathology].

PubMed

Heran Dreyfus, F; Galatoire, O; Koskas, P; Lafitte, F; Nau, E; Bergès, O

2016-11-01

Orbito-palpebral vascular pathology represents 10% of all the diseases of this area. The lesion may be discovered during a brain CT scan or MRI, or because it causes clinical symptoms such as orbital mass, visual or oculomotor alteration, pain, proptosis, or acute bleeding due to a complication of the lesion (hemorrhage, thrombosis). We present these lesions using an anatomical, clinical, imaging and therapeutic approach. We distinguish four different entities. Vascular tumors have common imaging characteristics (hypersignal on T2 sequence, contrast enhancement, abnormal vascularization well depicted with ultrasound and Doppler, and possible bleeding). The main lesions are cavernous hemangiomas, the most frequent lesion of that type during adulthood; infantile hemangiomas, the most frequent vascular tumor in children; and more seldomly, hemangioperitcytomas. True vascular malformations are divided according to their flow. Low flow lesions are venous (orbital varix), capillarovenous or lymphatic (lymphangioma). High flow malformations, more rare, are either arteriovenous or arterial malformations (aneurisms). Complex malformations include both low and high flow elements. Lesions leading to modifications of the orbito-palpebral blood flow are mainly due to cavernous sinus abnormalities, either direct carotid-cavernous fistula affecting young adults after severe head trauma, or dural fistula, more insidious, found in older adults. The last section is devoted to congenital syndromic vascular malformations (Sturge-Weber, Rendu-Olser…). This classification allows for a better understanding of these pathologies and their specific imaging features. Copyright © 2016. Published by Elsevier Masson SAS.

Phylostratigraphic profiles in zebrafish uncover chordate origins of the vertebrate brain.

PubMed

Šestak, Martin Sebastijan; Domazet-Lošo, Tomislav

2015-02-01

An elaborated tripartite brain is considered one of the important innovations of vertebrates. Other extant chordate groups have a more basic brain organization. For instance, cephalochordates possess a relatively simple brain possibly homologous to the vertebrate forebrain and hindbrain, whereas tunicates display the tripartite organization, but without the specialized brain centers. The difference in anatomical complexity is even more pronounced if one compares chordates with other deuterostomes that have only a diffuse nerve net or alternatively a rather simple central nervous system. To gain a new perspective on the evolutionary roots of the complex vertebrate brain, we made here a phylostratigraphic analysis of gene expression patterns in the developing zebrafish (Danio rerio). The recovered adaptive landscape revealed three important periods in the evolutionary history of the zebrafish brain. The oldest period corresponds to preadaptive events in the first metazoans and the emergence of the nervous system at the metazoan-eumetazoan transition. The origin of chordates marks the next phase, where we found the overall strongest adaptive imprint in almost all analyzed brain regions. This finding supports the idea that the vertebrate brain evolved independently of the brains within the protostome lineage. Finally, at the origin of vertebrates we detected a pronounced signal coming from the dorsal telencephalon, in agreement with classical theories that consider this part of the cerebrum a genuine vertebrate innovation. Taken together, these results reveal a stepwise adaptive history of the vertebrate brain where most of its extant organization was already present in the chordate ancestor. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Beyond tRNA cleavage: novel essential function for yeast tRNA splicing endonuclease unrelated to tRNA processing

PubMed Central

Dhungel, Nripesh; Hopper, Anita K.

2012-01-01

Pre-tRNA splicing is an essential process in all eukaryotes. In yeast and vertebrates, the enzyme catalyzing intron removal from pre-tRNA is a heterotetrameric complex (splicing endonuclease [SEN] complex). Although the SEN complex is conserved, the subcellular location where pre-tRNA splicing occurs is not. In yeast, the SEN complex is located at the cytoplasmic surface of mitochondria, whereas in vertebrates, pre-tRNA splicing is nuclear. We engineered yeast to mimic the vertebrate cell biology and demonstrate that all three steps of pre-tRNA splicing, as well as tRNA nuclear export and aminoacylation, occur efficiently when the SEN complex is nuclear. However, nuclear pre-tRNA splicing fails to complement growth defects of cells with defective mitochondrial-located splicing, suggesting that the yeast SEN complex surprisingly serves a novel and essential function in the cytoplasm that is unrelated to tRNA splicing. The novel function requires all four SEN complex subunits and the catalytic core. A subset of pre-rRNAs accumulates when the SEN complex is restricted to the nucleus, indicating that the SEN complex moonlights in rRNA processing. Thus, findings suggest that selection for the subcellular distribution of the SEN complex may reside not in its canonical, but rather in a novel, activity. PMID:22391451

Oxidative Stress, Unfolded Protein Response, and Apoptosis in Developmental Toxicity

PubMed Central

Kupsco, Allison; Schlenk, Daniel

2016-01-01

Physiological development requires precise spatiotemporal regulation of cellular and molecular processes. Disruption of these key events can generate developmental toxicity in the form of teratogenesis or mortality. The mechanism behind many developmental toxicants remains unknown. While recent work has focused on the unfolded protein response (UPR), oxidative stress, and apoptosis in the pathogenesis of disease, few studies have addressed their relationship in developmental toxicity. Redox regulation, UPR, and apoptosis are essential for physiological development and can be disturbed by a variety of endogenous and exogenous toxicants to generate lethality and diverse malformations. This review examines the current knowledge of the role of oxidative stress, UPR, and apoptosis in physiological development as well as in developmental toxicity, focusing on studies and advances in vertebrates model systems. PMID:26008783

[Cervical myelopathy from an aspect of a neurological surgeon].

PubMed

Koyama, T

1994-12-01

More than 65 per cent of intramedurally tumors and intradural extramedurally tumors were located in cervical region. They enact a cause of cervical myelopathy. A special attention should be paid to solitaly intramedurally vascular malformations, when the patients show an acute progressive myelopathy. In very rare cases of syringomyelia, intramedurally tumors such as hemangioblastoma or ependymoma could be found, so that enhanced MRI or angiography should be done if necessary. In cases of a herniated disc, cervical spondylosis and OPLL, the distance between articulo-pillar line and spinolaminal line must be measured. If the distance of both lines is near or the same, that means narrow cervical canal. In rare cases the form of the vertebral body is round. This is a rare cause of a type of narrow canal.

Fibroblast growth factor signaling in skeletal development and disease.

PubMed

Ornitz, David M; Marie, Pierre J

2015-07-15

Fibroblast growth factor (FGF) signaling pathways are essential regulators of vertebrate skeletal development. FGF signaling regulates development of the limb bud and formation of the mesenchymal condensation and has key roles in regulating chondrogenesis, osteogenesis, and bone and mineral homeostasis. This review updates our review on FGFs in skeletal development published in Genes & Development in 2002, examines progress made on understanding the functions of the FGF signaling pathway during critical stages of skeletogenesis, and explores the mechanisms by which mutations in FGF signaling molecules cause skeletal malformations in humans. Links between FGF signaling pathways and other interacting pathways that are critical for skeletal development and could be exploited to treat genetic diseases and repair bone are also explored. © 2015 Ornitz and Marie; Published by Cold Spring Harbor Laboratory Press.

The Smith-Lemli-Opitz syndrome

PubMed Central

Kelley, R.; Hennekam, R.

2000-01-01

The Smith-Lemli-Opitz syndrome (SLOS) is one of the archetypical multiple congenital malformation syndromes. The recent discovery of the biochemical cause of SLOS and the subsequent redefinition of SLOS as an inborn error of cholesterol metabolism have led to important new treatment possibilities for affected patients. Moreover, the recent recognition of the important role of cholesterol in vertebrate embryogenesis, especially with regard to the hedgehog embryonic signalling pathway and its effects on the expression of homeobox genes, has provided an explanation for the abnormal morphogenesis in the syndrome. The well known role of cholesterol in the formation of steroid hormones has also provided a possible explanation for the abnormal behavioural characteristics of SLOS.


Keywords: Smith-Lemli-Opitz syndrome; cholesterol metabolism; 7-dehydrocholesterol reductase; clinical history; management PMID:10807690

Mutations in extracellular matrix genes NID1 and LAMC1 cause autosomal dominant Dandy-Walker malformation and occipital cephaloceles.

PubMed

Darbro, Benjamin W; Mahajan, Vinit B; Gakhar, Lokesh; Skeie, Jessica M; Campbell, Elizabeth; Wu, Shu; Bing, Xinyu; Millen, Kathleen J; Dobyns, William B; Kessler, John A; Jalali, Ali; Cremer, James; Segre, Alberto; Manak, J Robert; Aldinger, Kimerbly A; Suzuki, Satoshi; Natsume, Nagato; Ono, Maya; Hai, Huynh Dai; Viet, Le Thi; Loddo, Sara; Valente, Enza M; Bernardini, Laura; Ghonge, Nitin; Ferguson, Polly J; Bassuk, Alexander G

2013-08-01

We performed whole-exome sequencing of a family with autosomal dominant Dandy-Walker malformation and occipital cephaloceles and detected a mutation in the extracellular matrix (ECM) protein-encoding gene NID1. In a second family, protein interaction network analysis identified a mutation in LAMC1, which encodes a NID1-binding partner. Structural modeling of the NID1-LAMC1 complex demonstrated that each mutation disrupts the interaction. These findings implicate the ECM in the pathogenesis of Dandy-Walker spectrum disorders. © 2013 WILEY PERIODICALS, INC.

Use of n-butyl cyanoacrylate to reduce left to right shunting of an abdominal arteriovenous malformation in a dog.

PubMed

Eason, B D; Hogan, D F; Lim, C; Hogan, M J

2017-08-01

A 9-month old castrated male Labradoodle presented to the cardiology service at Purdue University for evaluation of a low-grade murmur. Physical examination, thoracic radiography, and echocardiography were strongly supportive of an extracardiac left-to-right shunt. Subsequent evaluation with nuclear scintigraphy and computed tomography angiography revealed a large, complex arteriovenous malformation within the cranial abdomen. Staged interventional attenuation of the shunt was performed using n-butyl cyanoacrylate that resulted in a reduction in echocardiographic and nuclear scintigraphy derived shunt estimation. Copyright © 2017 Elsevier B.V. All rights reserved.

Juxtaposed Polycomb complexes co-regulate vertebral identity.

PubMed

Kim, Se Young; Paylor, Suzanne W; Magnuson, Terry; Schumacher, Armin

2006-12-01

Best known as epigenetic repressors of developmental Hox gene transcription, Polycomb complexes alter chromatin structure by means of post-translational modification of histone tails. Depending on the cellular context, Polycomb complexes of diverse composition and function exhibit cooperative interaction or hierarchical interdependency at target loci. The present study interrogated the genetic, biochemical and molecular interaction of BMI1 and EED, pivotal constituents of heterologous Polycomb complexes, in the regulation of vertebral identity during mouse development. Despite a significant overlap in dosage-sensitive homeotic phenotypes and co-repression of a similar set of Hox genes, genetic analysis implicated eed and Bmi1 in parallel pathways, which converge at the level of Hox gene regulation. Whereas EED and BMI1 formed separate biochemical entities with EzH2 and Ring1B, respectively, in mid-gestation embryos, YY1 engaged in both Polycomb complexes. Strikingly, methylated lysine 27 of histone H3 (H3-K27), a mediator of Polycomb complex recruitment to target genes, stably associated with the EED complex during the maintenance phase of Hox gene repression. Juxtaposed EED and BMI1 complexes, along with YY1 and methylated H3-K27, were detected in upstream regulatory regions of Hoxc8 and Hoxa5. The combined data suggest a model wherein epigenetic and genetic elements cooperatively recruit and retain juxtaposed Polycomb complexes in mammalian Hox gene clusters toward co-regulation of vertebral identity.

Ensembl genomes 2016: more genomes, more complexity

USDA-ARS?s Scientific Manuscript database

Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the context of the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent...

Vascular anomalies and the growth of limbs: a review.

PubMed

Enjolras, Odile; Chapot, René; Merland, Jean Jacques

2004-11-01

Growth of the limb in a child can be impaired, with the coexistence of a vascular malformation. In these vascular bone syndromes, altered growth is manifest as overgrowth or hypotrophy. The vascular malformation is usually complex and gets progressively worse with time. The two types of vascular anomalies in limbs, fast-flow and slow-flow, can be associated with limb length discrepancies. The fast-flow vascular malformations together with arteriovenous fistulae are part of Parkes Weber syndrome, characterized by congenital red cutaneous staining, hypertrophy in girth and increasing of limb length, lymphedema, increasing skin alterations due to a distal vascular steal, and pain, all of which develop during childhood. Treatment is generally conservative. An affected lower extremity can be complicated by pelvic tilting and scoliosis because leg length discrepancy may reach 10 cm. To avoid such a course, stapling epiphysiodesis of the knee cartilages is often performed, but this orthopedic procedure may augment the worsening of the arterial venous malformation in the limb. Therefore, less aggressive orthopedic management is preferable. Slow-flow vascular anomalies associated with limb growth alteration include (1) a diffuse capillary malformation (port-wine stain) with congenital hypertrophy of the involved extremity which is non-progressive; (2) purely venous malformations invading skin, muscles and joints, with pain, functional impairment, a chronic localized intravascular coagulopathy requiring distinctive management, and usually a slight undergrowth of the affected extremity and progressing amyotrophy; (3) the triad of a port-wine stain, anomalous veins and overgrowth of the limb, often known as Klippel-Trenaunay syndrome, which requires orthopedic management to decide the optimal timing for epiphysiodesis (i.e. when leg length discrepancy is >2.5 cm). Varicose veins are sometimes surgically removed after ultrasonographic and Doppler evaluation has confirmed a normal deep venous system. Capillary malformations can be effectively treated with pulsed dye laser, but results are usually poor in distal extremities.

Computational and Organotypic Modeling of Microcephaly (Teratology Society)

EPA Science Inventory

Microcephaly is associated with reduced cortical surface area and ventricular dilations. Many genetic and environmental factors precipitate this malformation, including prenatal alcohol exposure and maternal Zika infection. This complexity motivates the engineering of computation...

Molecular evolutionary analysis of vertebrate transducins: a role for amino acid variation in photoreceptor deactivation.

PubMed

Lin, Yi G; Weadick, Cameron J; Santini, Francesco; Chang, Belinda S W

2013-12-01

Transducin is a heterotrimeric G protein that plays a critical role in phototransduction in the rod and cone photoreceptor cells of the vertebrate retina. Rods, highly sensitive cells that recover from photoactivation slowly, underlie dim-light vision, whereas cones are less sensitive, recover more quickly, and underlie bright-light vision. Transducin deactivation is a critical step in photoreceptor recovery and may underlie the functional distinction between rods and cones. Rods and cones possess distinct transducin α subunits, yet they share a common deactivation mechanism, the GTPase activating protein (GAP) complex. Here, we used codon models to examine patterns of sequence evolution in rod (GNAT1) and cone (GNAT2) α subunits. Our results indicate that purifying selection is the dominant force shaping GNAT1 and GNAT2 evolution, but that GNAT2 has additionally been subject to positive selection operating at multiple phylogenetic scales; phylogeny-wide analysis identified several sites in the GNAT2 helical domain as having substantially elevated dN/dS estimates, and branch-site analysis identified several nearby sites as targets of strong positive selection during early vertebrate history. Examination of aligned GNAT and GAP complex crystal structures revealed steric clashes between several positively selected sites and the deactivating GAP complex. This suggests that GNAT2 sequence variation could play an important role in adaptive evolution of the vertebrate visual system via effects on photoreceptor deactivation kinetics and provides an alternative perspective to previous work that focused instead on the effect of GAP complex concentration. Our findings thus further the understanding of the molecular biology, physiology, and evolution of vertebrate visual systems.

The origin and evolution of the ectodermal placodes

PubMed Central

Graham, Anthony; Shimeld, Sebastian M

2013-01-01

Many of the features that distinguish the vertebrates from other chordates are found in the head. Prominent amongst these differences are the paired sense organs and associated cranial ganglia. Significantly, these structures are derived developmentally from the ectodermal placodes. It has therefore been proposed that the emergence of the ectodermal placodes was concomitant with and central to the evolution of the vertebrates. More recent studies, however, indicate forerunners of the ectodermal placodes can be readily identified outside the vertebrates, particularly in urochordates. Thus the evolutionary history of the ectodermal placodes is deeper and more complex than was previously appreciated with the full repertoire of vertebrate ectodermal placodes, and their derivatives, being assembled over a protracted period rather than arising collectively with the vertebrates. PMID:22512454

NATURE OF CUMULATIVE IMPACTS ON BIOTIC DIVERSITY OF WETLAND VERTEBRATES

EPA Science Inventory

There is no longer any doubt that cumulative impacts have important effects on wetland vertebrates. he interactions of species diversity and community structure produce a complex pattern in which environmental impacts can play a highly significant role. ariety of examples shows h...

Congenital cervical kyphosis in two young sighthounds.

PubMed

Forterre, F; Casoni, D; Tomek, A; Karli, P; Howard, J; Precht, C

2015-01-01

Cervical vertebral (C) malformation is rarely reported in large breed dogs. Congenital cervical kyphosis (CCK) may result from defects of vertebral segmentation, failure of formation or both. This report describes two cases of C3-C4 CCK in young sighthounds, treated surgically. An 18-month-old female Deerhound and a six-week-old female Borzoi dog were presented because of the complaints of reluctance to exercise and signs of of neck pain. Both dogs were neurologically normal. Diagnostic imaging revealed C3-C4 deformity, moderate kyphosis, and spinal canal stenosis associated with chronic spinal cord pressure atrophy. Both dogs underwent surgical treatment. A staged two-step surgery starting with dorsal decompression was elected in the Deerhound. After the first surgical procedure, the dog developed focal myelomalacia and phrenic nerve paralysis and was euthanatized. A ventral distraction-fusion technique with two locking plates was performed in the Borzoi. This patient recovered uneventfully and long-term follow-up computed tomography revealed complete spondylodesis. Until now, CCK has only been described in sighthounds. Congenital cervical kyphosis might be considered a differential diagnosis in these breeds that are presented with signs of cervical pain. Ventral realignment-fusion and bone grafting may be considered for surgical treatment, although the earliest age at which this procedure can and should be performed remains unclear.

Vertebrate Genome Evolution in the Light of Fish Cytogenomics and rDNAomics

PubMed Central

Howell, W. Mike

2018-01-01

To understand the cytogenomic evolution of vertebrates, we must first unravel the complex genomes of fishes, which were the first vertebrates to evolve and were ancestors to all other vertebrates. We must not forget the immense time span during which the fish genomes had to evolve. Fish cytogenomics is endowed with unique features which offer irreplaceable insights into the evolution of the vertebrate genome. Due to the general DNA base compositional homogeneity of fish genomes, fish cytogenomics is largely based on mapping DNA repeats that still represent serious obstacles in genome sequencing and assembling, even in model species. Localization of repeats on chromosomes of hundreds of fish species and populations originating from diversified environments have revealed the biological importance of this genomic fraction. Ribosomal genes (rDNA) belong to the most informative repeats and in fish, they are subject to a more relaxed regulation than in higher vertebrates. This can result in formation of a literal ‘rDNAome’ consisting of more than 20,000 copies with their high proportion employed in extra-coding functions. Because rDNA has high rates of transcription and recombination, it contributes to genome diversification and can form reproductive barrier. Our overall knowledge of fish cytogenomics grows rapidly by a continuously increasing number of fish genomes sequenced and by use of novel sequencing methods improving genome assembly. The recently revealed exceptional compositional heterogeneity in an ancient fish lineage (gars) sheds new light on the compositional genome evolution in vertebrates generally. We highlight the power of synergy of cytogenetics and genomics in fish cytogenomics, its potential to understand the complexity of genome evolution in vertebrates, which is also linked to clinical applications and the chromosomal backgrounds of speciation. We also summarize the current knowledge on fish cytogenomics and outline its main future avenues. PMID:29443947

Diprosopus (partially duplicated head) associated with anencephaly: a case report.

PubMed

al Muti Zaitoun, A; Chang, J; Booker, M

1999-01-01

Craniofacial duplication (diprosopus) is a rare form of conjoined twin. A 16 year old mother with a twin pregnancy delivered one normally formed baby boy and one diprosopus male. The malformed baby was 33 weeks of gestation with a single trunk, normal limbs and various degrees of facial duplication. Of the following structures there were two of each: noses, eyes, ears (and one dimple), mouths, tongues and, with bilateral central cleft lips and cleft palates. This was associated with holoprosencephaly and craniorachischisis. Internal organs showed no duplication. There were multiple congenital anomalies including diaphragmatic hernia, small lungs, two lobes of the right lung, ventricular septal defect, small adrenal gland and small left kidney with short ureter. The body also had a short neck, small chest cavities and kyphosis. X-ray revealed duplication of the vertebral column. The case presented here represents a type II of diprosopia of Rating (1933) and is the least common type reported. We also reviewed 22 recently reported cases of diprosopus. In addition to facial duplication, anencephaly, neural tube defect and cardiac malformations represent the more common congenital abnormalities associated with diprosopus. The pathogenesis of diprosopus is not well understood. Factors that play a role in diprosopus are probably similar to those factors (genetic, environmental and abnormal placental circulation) which affect monozoygotic twins as observed in this case report. Early ultrasonography diagnosis of diprosopus permits one to consider a vaginal therapeutic abortion.

Pathological findings in dicephalus dipus dibrachius: implications for mechanisms in two pairs of lateral conjoined twins.

PubMed

Itoh, K; Imai, Y; Obayashi, C; Hayashi, Y; Hanioka, K; Itoh, H

1993-06-01

The anatomical and pathological features of two pairs of dicephalic conjoined twins (case 1 and 2) are described. Both twins showed duplicitas lateralis representing diprosopus dipus dibrachius. There were two complete heads on two necks, one thorax, one abdomen and externally normal two arms and two legs. Case 1 showed dicephalus with anencephaly, two vertebral columns and two spinal cords, which converged from the thoracic region distally. The esophagus, stomachs and partial small intestines were duplicated, which fused at yolk sac (with Meckel's diverticulum). The heart was incompletely fused. The lungs and trachea were doubled. Two spinal cords were fused from the thoracic region caudally and showed myelomeningocele and Arnold-Chiari malformation in case 2. Two larynxes and two thracheas connected with the incompletely fused three lobes of lungs. The conjoined lungs were hypoplastic. The heart was single, showing ventral septal defect, transposition of great arteries, two cuspid aortic valves and preductal aortic coarctation. The duplicated esophagi were conjoined in Y-shape and single stomach, duodenum, intestine and colon were found. There were pairs of kidneys, adrenal glands and ureters and single female genitalia in both cases. These findings indicate that the craniocaudal paleoaxes were separated in the cranial region and converted or fused under the thoracic region like a Y-shape. Further development defects and deformations might be important factors to form malformations in these case.

Incidental occlusion of anterior spinal artery due to Onyx reflux in embolization of spinal type II arteriovenous malformation.

PubMed

Kim, Joohyun; Lee, Jang-Bo; Cho, Tai-Hyoung; Hur, Junseok W

2017-05-01

Onyx embolization is one of the standard treatments for brain arteriovenous malformations (AVMs) and is a promising method for spinal AVMs as well. Its advantages have been emphasized, and few complications have been reported with Onyx embolization in spinal AVMs. Here, we report an incidental anterior spinal artery (ASA) occlusion due to Onyx reflux during embolization of a spinal type II AVM. A 15-year-old boy presented with weakness in both upper and lower extremities. Magnetic resonance imaging and spinal angiogram revealed a spinal type II AVM with two feeders including the right vertebral artery (VA) and the right deep cervical artery. Onyx embolization was performed gradually from the VA to the deep cervical artery and an unexpected Onyx reflux to the ASA was observed during the latter stage deep cervical artery embolization. Post-operative quadriplegia and low cranial nerves (CN) dysfunction were observed. Rehabilitation treatment was performed and the patient showed marked improvement of neurologic deterioration at 1-year follow-up. Onyx is an effective treatment choice for spinal AVMs. However, due to the small vasculature of the spine compared to the brain, the nidus is rapidly packed with a small amount of Onyx, which allows Onyx reflux to unexpected vessels. Extreme caution is required and dual-lumen balloon catheter could be considered for Onyx embolization in spinal AVMs treatment.

Compound Heterozygosity for Null Mutations and a Common Hypomorphic Risk Haplotype in TBX6 Causes Congenital Scoliosis.

PubMed

Takeda, Kazuki; Kou, Ikuyo; Kawakami, Noriaki; Iida, Aritoshi; Nakajima, Masahiro; Ogura, Yoji; Imagawa, Eri; Miyake, Noriko; Matsumoto, Naomichi; Yasuhiko, Yukuto; Sudo, Hideki; Kotani, Toshiaki; Nakamura, Masaya; Matsumoto, Morio; Watanabe, Kota; Ikegawa, Shiro

2017-03-01

Congenital scoliosis (CS) occurs as a result of vertebral malformations and has an incidence of 0.5-1/1,000 births. Recently, TBX6 on chromosome 16p11.2 was reported as a disease gene for CS; about 10% of Chinese CS patients were compound heterozygotes for rare null mutations and a common haplotype defined by three SNPs in TBX6. All patients had hemivertebrae. We recruited 94 Japanese CS patients, investigated the TBX6 locus for both mutations and the risk haplotype, examined transcriptional activities of mutant TBX6 in vitro, and evaluated clinical and radiographic features. We identified TBX6 null mutations in nine patients, including a missense mutation that had a loss of function in vitro. All had the risk haplotype in the opposite allele. One of the mutations showed dominant negative effect. Although all Chinese patients had one or more hemivertebrae, two Japanese patients did not have hemivertebra. The compound heterozygosity of null mutations and the common risk haplotype in TBX6 also causes CS in Japanese patients with similar incidence. Hemivertebra was not a specific type of spinal malformation in TBX6-associated CS (TACS). A heterozygous TBX6 loss-of-function mutation has been reported in a family with autosomal-dominant spondylocostal dysostosis, but it may represent a spectrum of the same disease with TACS. © 2017 WILEY PERIODICALS, INC.

Size and Cell Number of the Utricle in kinetotically swimming Fish: A parabolic Aircraft Flight Study

NASA Astrophysics Data System (ADS)

Baeuerle, A.; Anken, R.; Baumhauer, N.; Hilbig, R.; Rahmann, H.

Humans taking part in parabolic aircraft flights (PAFs) may suffer from space motion sickness (SMS, a kinetosis). Since it has been repeatedly shown earlier that some fish of a given batch also reveal a kinetotic behaviour during PAFs (especially so-called spinning movements and looping responses), and due to the homology of the vestibular apparatus among all vertebrates, fish can be used as model systems to investigate the origin of susceptibility to motion sickness. Therefore, we examined the utricular maculae (they are responsible for the internalisation of gravity in teleosteans) of fish swimming kinetotically during the μg-phases in the course of PAFs in comparison with animals from the same batch who swam normally. On the light microscopical level, it was found that the total number of both sensory and supporting cells of the utricular maculae did not differ between kinetotic animals as compared to normally swimming fish. Cell density (sensory and supporting cells/100μm -μm), however, was reduced in kinetotic animals (p<0.0001), which seemed to be due to malformed epithelial cells (increase in cell size) of the kinetotic specimens. Susceptibility to kinetoses may therefore originate in asymmetric inner ear otoliths as has been suggested earlier, but also in genetically predispositioned, malformed sensory epithelia. This work was financially supported by the German Aerospace Center (DLR) e.V. (FKZ: 50 WB 9997).

A Syndromic Neurodevelopmental Disorder Caused by De Novo Variants in EBF3.

PubMed

Chao, Hsiao-Tuan; Davids, Mariska; Burke, Elizabeth; Pappas, John G; Rosenfeld, Jill A; McCarty, Alexandra J; Davis, Taylor; Wolfe, Lynne; Toro, Camilo; Tifft, Cynthia; Xia, Fan; Stong, Nicholas; Johnson, Travis K; Warr, Coral G; Yamamoto, Shinya; Adams, David R; Markello, Thomas C; Gahl, William A; Bellen, Hugo J; Wangler, Michael F; Malicdan, May Christine V

2017-01-05

Early B cell factor 3 (EBF3) is a member of the highly evolutionarily conserved Collier/Olf/EBF (COE) family of transcription factors. Prior studies on invertebrate and vertebrate animals have shown that EBF3 homologs are essential for survival and that loss-of-function mutations are associated with a range of nervous system developmental defects, including perturbation of neuronal development and migration. Interestingly, aristaless-related homeobox (ARX), a homeobox-containing transcription factor critical for the regulation of nervous system development, transcriptionally represses EBF3 expression. However, human neurodevelopmental disorders related to EBF3 have not been reported. Here, we describe three individuals who are affected by global developmental delay, intellectual disability, and expressive speech disorder and carry de novo variants in EBF3. Associated features seen in these individuals include congenital hypotonia, structural CNS malformations, ataxia, and genitourinary abnormalities. The de novo variants affect a single conserved residue in a zinc finger motif crucial for DNA binding and are deleterious in a fly model. Our findings indicate that mutations in EBF3 cause a genetic neurodevelopmental syndrome and suggest that loss of EBF3 function might mediate a subset of neurologic phenotypes shared by ARX-related disorders, including intellectual disability, abnormal genitalia, and structural CNS malformations. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Metamerism in cephalochordates and the problem of the vertebrate head.

PubMed

Onai, Takayuki; Adachi, Noritaka; Kuratani, Shigeru

2017-01-01

The vertebrate head characteristically exhibits a complex pattern with sense organs, brain, paired eyes and jaw muscles, and the brain case is not found in other chordates. How the extant vertebrate head has evolved remains enigmatic. Historically, there have been two conflicting views on the origin of the vertebrate head, segmental and non-segmental views. According to the segmentalists, the vertebrate head is organized as a metameric structure composed of segments equivalent to those in the trunk; a metamere in the vertebrate head was assumed to consist of a somite, a branchial arch and a set of cranial nerves, considering that the head evolved from rostral segments of amphioxus-like ancestral vertebrates. Non-segmentalists, however, considered that the vertebrate head was not segmental. In that case, the ancestral state of the vertebrate head may be non-segmented, and rostral segments in amphioxus might have been secondarily gained, or extant vertebrates might have evolved through radical modifications of amphioxus-like ancestral vertebrate head. Comparative studies of mesodermal development in amphioxus and vertebrate gastrula embryos have revealed that mesodermal gene expressions become segregated into two domains anteroposteriorly to specify the head mesoderm and trunk mesoderm only in vertebrates; in this segregation, key genes such as delta and hairy, involved in segment formation, are expressed in the trunk mesoderm, but not in the head mesoderm, strongly suggesting that the head mesoderm of extant vertebrates is not segmented. Taken together, the above finding possibly adds a new insight into the origin of the vertebrate head; the vertebrate head mesoderm would have evolved through an anteroposterior polarization of the paraxial mesoderm if the ancestral vertebrate had been amphioxus-like.

Comparative anatomy of the vestibular nuclear complex in submammalian vertebrates.

NASA Technical Reports Server (NTRS)

Mehler, W. R.

1972-01-01

A synopsis of the literature on the natural history of the vestibular nuclear complex (VNC) in lower vertebrates is presented in an attempt to assess the knowledge available. The review discloses that there is considerable descriptive information that is widely dispersed in the literature. However, information about the topology, number, and cellular composition of the cell groups that compose the VNC is sketchy. Major cytological and hodological information is still needed to establish which parts of the VNC actually are homologous.

Total anomalous pulmonary venous connection and a constellation of craniofacial, skeletal, and urogenital anomalies in a newborn and similar features in his 36-year-old father.

PubMed

Pierson, D M; Taboada, E M; Lofland, G K; Begleiter, M L; Smith, G S; Hall, F; Butler, M G

2001-04-01

We report on a newborn male born to non-consanguineous parents with total anomalous pulmonary venous connection (TAPVC) and additional findings of malformed ears, hypertelorism, brachyphalangy in the hands, pterygium of the elbows, knees, and wrists, complex lower limb pre-axial polydactyly, tibial shortening, clubfeet, horseshoe kidney and a micropenis. He had a 46,XY karyotype. His 36-year-old father had similar craniofacial and limb anomalies suggesting an autosomal dominant syndrome with variable expression. Our patients may represent the 3rd and 4th examples of a newly-described syndrome by Baraitser et al. [(1997) Clin Dysmorphol 6:111-121] which is distinguished by malformed ears, complex pre-axial polydactyly and tibial aplasia in the lower limbs, severe brachyphalangy in the hands, and a micropenis.

Clinical, functional, and neurophysiologic assessment of dysplastic cortical networks: Implications for cortical functioning and surgical management.

PubMed

Duchowny, Michael

2009-10-01

Cortical malformations are highly epileptogenic lesions associated with complex, unanticipated, and often aberrant electrophysiologic and functional relationships. These relationships are inextricably linked to widespread cortical networks subserving eloquent functions, particularly language and motor ability. Cytomegalic neurons but not balloon cells in Palmini type 2 dysplastic cortex are intrinsically hyperexcitable and contribute to local epileptogenesis and functional responsiveness. However, there is much evidence that focal cortical dysplasia is rarely a localized or even regional process, and is a functionally, electrophysiologically, and ultimately clinically integrated neural network disorder. Not surprisingly, malformed cortex is implicated in cognitive dysfunction, particularly disturbances of linguistic processing. An understanding of these relationships is critical for successful epilepsy surgery. Gains in surgical prognosis rely on multiple diagnostic modalities to delineate complex anatomic, electrophysiologic, and functional relationships in magnetic resonance imaging (MRI)-negative patients with rates of seizure-freedom roughly comparable to lesional patients.

Distinct modes of recruitment of the CCR4-NOT complex by Drosophila and vertebrate Nanos.

PubMed

Raisch, Tobias; Bhandari, Dipankar; Sabath, Kevin; Helms, Sigrun; Valkov, Eugene; Weichenrieder, Oliver; Izaurralde, Elisa

2016-05-02

Nanos proteins repress the expression of target mRNAs by recruiting effector complexes through non-conserved N-terminal regions. In vertebrates, Nanos proteins interact with the NOT1 subunit of the CCR4-NOT effector complex through a NOT1 interacting motif (NIM), which is absent in Nanos orthologs from several invertebrate species. Therefore, it has remained unclear whether the Nanos repressive mechanism is conserved and whether it also involves direct interactions with the CCR4-NOT deadenylase complex in invertebrates. Here, we identify an effector domain (NED) that is necessary for the Drosophila melanogaster (Dm) Nanos to repress mRNA targets. The NED recruits the CCR4-NOT complex through multiple and redundant binding sites, including a central region that interacts with the NOT module, which comprises the C-terminal domains of NOT1-3. The crystal structure of the NED central region bound to the NOT module reveals an unanticipated bipartite binding interface that contacts NOT1 and NOT3 and is distinct from the NIM of vertebrate Nanos. Thus, despite the absence of sequence conservation, the N-terminal regions of Nanos proteins recruit CCR4-NOT to assemble analogous repressive complexes. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

[Complex program for the recovery of the vertebral column motor function].

PubMed

Kukareko, V P; Furmanov, A G

2011-01-01

This paper addresses the problems pertinent to the improvement of the efficacy of restoration of the vertebral column motor function based on the implementation of a comprehensive therapeutic program including massage, thermal procedures, and physical exercises. The program was realized in three phases, viz. preparatory, basic, and consolidating. The results of integral estimation of the whole body and vertebral column condition were taken into consideration. The experiment lasted 6 months and confirmed high efficiency of the comprehensive program.

Reduced Field of View Diffusion-Weighted Imaging in the Evaluation of Congenital Spine Malformations.

PubMed

Radhakrishnan, Rupa; Betts, Aaron M; Care, Marguerite M; Serai, Suraj; Zhang, Bin; Jones, Blaise V

2016-05-01

Reduced field of view diffusion-weighted imaging (rFOV DWI) is a more recently described technique in the evaluation of spine pathology. In adults, this technique has been shown to increase clinician confidence in identification of diffusion restricting lesions. In this study, we evaluate the image quality and diagnostic confidence of the rFOV DWI technique in pediatric spine MRI. We included patients with MRI of the lumbar spine for suspected congenital abnormalities who had conventional SS-EPI (single shot echo planar imaging) with full field of view (fFOV) and rFOV DWI performed. Images were graded for image quality and observer confidence for detection of lesions with reduced diffusion. Position of the conus and L3 vertebral body measurements were recorded. Comparisons were made between the fFOV and rFOV scores. Fifty children (30 girls, 20 boys) were included (median 3.6 years). Compared to the fFOV images, the rFOV images scored higher in image quality (P < 0.0001) and for confidence in detecting lesions with reduced diffusion (P < 0.0001). The average spread of identified conus position was smaller for in rFOV compared to fFOV (P = 0.0042). There was no significant difference in the L3 vertebral body measurements between the two methods. In rFOV, the anterior aspects of the vertebral bodies were excluded in a few studies due to narrow FOV. rFOV DWI of the lumbar spine in the pediatric population has qualitatively improved image quality and observer confidence for lesion detection when compared to conventional fFOV SS-EPI DWI. Copyright © 2015 by the American Society of Neuroimaging.

Ultrasonographic diagnosis of Jarcho-Levin syndrome at 20 weeks' gestation in a fetus without previous family history.

PubMed

del Río Holgado, María; Martínez, Josep M; Gómez, Olga; Casals, Gemma; Bargalló, Nuria; Fortuny, Albert; Puerto, Bienvenido

2005-01-01

Jarcho-Levin syndrome (JLS; spondylothoracic dysplasia) is a congenital disease characterized by multiple vertebral and rib malformations, causing a short trunk dwarfism commonly leading to respiratory insufficiency and death during the first years of life. We describe a case diagnosed during the second trimester routine ultrasound scan for screening of fetal anomalies without a previous family history. The fetus had a severe disorganization of the spine and ribs, skeletal kyphosis, with several hemivertebrae and a small thorax. All of the findings at postmortem examination confirmed the ultrasound features and were consistent with the JLS. To the best of our knowledge there is only one case reported in the literature of a prenatal diagnosis of the syndrome in a family with low risk for the condition. Copyright (c) 2005 S. Karger AG, Basel.

Emerging phleboviruses.

PubMed

Elliott, Richard M; Brennan, Benjamin

2014-04-01

The Bunyavidae family is the largest grouping of RNA viruses and arguably the most diverse. Bunyaviruses have a truly global distribution and can infect vertebrates, invertebrates and plants. The majority of bunyaviruses are vectored by arthropods and thus have the remarkable capability to replicate in hosts of disparate phylogeny. The family has provided many examples of emerging viruses including Sin Nombre and related viruses responsible for hantavirus cardiopulmonary syndrome in the Americas, first identified in 1993, and Schmallenberg virus which emerged in Europe in 2011, causing foetal malformations in ruminants. In addition, some well-known bunyaviruses like Rift Valley fever and Crimean-Congo haemorrhagic fever viruses continue to emerge in new geographical locations. In this short review we focus on newly identified viruses associated with severe haemorrhagic disease in humans in China and the US. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Question mark ears, temporo-mandibular joint malformation and hypotonia: auriculo-condylar syndrome or a distinct entity?

PubMed

Priolo, M; Lerone, M; Rosaia, L; Calcagno, E P; Sadeghi, A K; Ghezzi, F; Ravazzolo, R; Silengo, M

2000-10-01

We report a boy with prominent, peculiarly malformed ears, abnormality of the ramus of the mandible and hypotonia. An isolated peculiar bilateral ear deformity named 'question mark ear' has been delineated in plastic reconstruction surgery reviews [Cosman et al., 1970 Plast Reconstr Surg 46:454-457; Cosman (1984) Plast Reconstr Surg 73:572-576; Takato et al. (1989) Ann Plast Surg 22:69-73; Brodovsky (1997) Plast Reconstr Surg 100:1254-1257; Park (1998) Plast Reconstr Surg 101:1620-1623; Al-Quattan (1998) Plast Reconstr Surg 102:439-441] and a similar deformity of the ear and changes in the temporo-mandibular joint and condyle has been described by Jampol et al. [(1998) Am J Med Genet 75:449-452] and by Guion-Almeida et al. [(1999) Am J Med Genet 86:130-133]. The present case may be the third description of this malformation complex with additional clinical features characterized by hypotonia and mild developmental delay, or possibly a new distinct entity.

"Acquired" Dandy-Walker malformation and cerebellar hemorrhage: Usefulness of serial MRI.

PubMed

Pichiecchio, Anna; Decio, Alice; Di Perri, Carol; Parazzini, Cecilia; Rossi, Andrea; Signorini, Sabrina

2016-01-01

Neuroimaging plays a fundamental role in the diagnosis of Dandy Walker malformation (DWM), a posterior fossa anomaly that is usually associated with genetic abnormalities, but may rarely be ascribed to acquired causes. Here, we report the clinical history and neuroimaging studies of a child with a complex cardiac malformation, developmental delay, and oculomotor anomalies whose neuroimaging findings were consistent with an acquired form of DWM. Fetal MRI at gestational weeks 27 and 31 showed cerebellar and vermis hypoplasia and fourth ventricle enlargement, together with hemosiderin deposits on the cerebellar hemispheric surface, but without significant vermian rotation. Postnatal MRIs at 5 days and 13 months revealed progressive counter-clockwise rotation of the hypoplastic cerebellar vermis with cystic dilation of the fourth ventricle, eventually leading to a full-blown DWM. This case strengthens the opinion that DWM is a heterogeneous condition, and may support the hypothesis that acquired meningeal abnormalities in the form of cortico-pial hemosiderosis may play a role in the development of DWM. This case also demonstrates that serial neuroimaging plays a key role in the correct diagnosis of posterior fossa malformations, whose prognosis is difficult to establish on second trimester fetal MRI and requires longer clinical follow-up. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Long-Term Habituation of the C-Start Escape Response in Zebrafish Larvae

PubMed Central

Roberts, Adam C.; Pearce, Kaycey C.; Choe, Ronny C.; Alzagatiti, Joseph B.; Yeung, Anthony K.; Bill, Brent R.; Glanzman, David L.

2016-01-01

The cellular and molecular basis of long-term memory in vertebrates remains poorly understood. Knowledge regarding long-term memory has been impeded by the enormous complexity of the vertebrate brain, particularly the mammalian brain, as well as by the relative complexity of the behavioral alterations examined in most studies of long-term memory in vertebrates. Here, we demonstrate a long-term form of nonassociative learning—specifically, long-term habituation (LTH)—of a simple reflexive escape response, the C-start, in zebrafish larvae. The C-start is triggered by the activation of one of a pair of giant neurons in the zebrafish’s hindbrain, the Mauthner cells. We show that LTH of the C-start requires the activity of NMDA receptors and involves macromolecular synthesis. We further show that the long-term habituated reflex can by rapidly dishabituated by a brief tactile stimulus. Our results set the stage for rigorous, mechanistic investigations of the long-term memory for habituation of a reflexive behavioral response, one that is mediated by a relatively simple, neurobiologically tractable, neural circuit. Moreover, the demonstration of NMDAR and transcriptionally dependent LTH in a translucent vertebrate organism should facilitate the use of optical recording, and optogenetic manipulation, of neuronal activity to elucidate the cellular basis of a long-term vertebrate memory. PMID:27555232

Clinical Characteristics of Patients Who Underwent Surgery for Genital Tract Malformations at Peking Union Medical College Hospital across 31 Years.

PubMed

Wang, Guang-Han; Zhu, Lan; Liu, Ai-Ming; Xu, Tao; Lang, Jing-He

2016-10-20

Female genital malformations represent miscellaneous deviations from normal anatomy. This study aimed to explore the clinical characteristics of patients who underwent surgery for genital tract malformations at Peking Union Medical College Hospital (PUMCH) during a 31-year period. We retrospectively reviewed surgical cases of congenital malformation of the female genital tract at PUMCH for a 31-year period, analyzed the clinical characteristics of 1634 hospitalized patients, and investigated their general condition, diagnosis, and treatment process. The average patient age was 27.6 ± 9.9 years. The average ages of patients who underwent surgery for uterine malformation and vaginal malformation were 31.9 ± 8.8 years and 24.7 ± 9.0 years, respectively; these ages differed significantly (P < 0.01). Among patients with genital tract malformation, the percentages of vaginal malformation, uterine malformation, vulva malformation, cervical malformation, and other malformations were 43.9%, 43.5%, 7.4%, 2.3%, and 2.8%, respectively. Among patients with uterine malformation, 34.5% underwent surgery for the genital tract malformation, whereas in patients with vaginal malformation, the proportion is 70.6%; the difference between the two groups was statistically significant (P < 0.01). The percentage of complications of the urinary system in patients with vaginal malformations was 10.2%, which was statistically significantly higher than that (5.3%) in patients with uterine malformations (P < 0.01). Compared to patients with uterine malformations, patients with vaginal malformations displayed more severe clinical symptoms, a younger surgical age, and a greater need for attention, early diagnosis, and treatment. Patients with genital tract malformations, particularly vaginal malformations, tend to have more complications of the urinary system and other malformations than patients with uterine malformations.

Comparative genetic diversity of Lyme disease bacteria in Northern Californian ticks and their vertebrate hosts.

PubMed

Swei, Andrea; Bowie, Verna C; Bowie, Rauri C K

2015-04-01

Vector-borne pathogens are transmitted between vertebrate hosts and arthropod vectors, two immensely different environments for the pathogen. There is further differentiation among vertebrate hosts that often have complex, species-specific immunological responses to the pathogen. All this presents a heterogeneous environmental and immunological landscape with possible consequences on the population genetic structure of the pathogen. We evaluated the differential genetic diversity of the Lyme disease pathogen, Borrelia burgdorferi, in its vector, the western black-legged tick (Ixodes pacificus), and in its mammal host community using the 5S-23S rRNA intergenic spacer region. We found differences in haplotype distribution of B. burgdorferi in tick populations from two counties in California as well as between a sympatric tick and vertebrate host community. In addition, we found that three closely related haplotypes consistently occurred in high frequency in all sample types. Lastly, our study found lower species diversity of the B. burgdorferi species complex, known as B. burgdorferi sensu lato, in small mammal hosts versus the tick populations in a sympatric study area. Copyright © 2015 Elsevier GmbH. All rights reserved.

The Australian scincid lizard Menetia greyii: a new instance of widespread vertebrate parthenogenesis.

PubMed

Adams, Mark; Foster, Ralph; Hutchinson, Mark N; Hutchinson, Rhonda G; Donnellan, Steve C

2003-11-01

Molecular data derived from allozymes and mitochondrial nucleotide sequences, in combination with karyotypes, sex ratios, and inheritance data, have revealed the widespread Australian lizard Menetia greyii to be a complex of sexual and triploid unisexual taxa. Three sexual species, three presumed parthenogenetic lineages, and one animal of uncertain status were detected amongst 145 animals examined from south-central Australia, an area representing less than one-seventh of the total distribution of the complex. Parthenogenesis appears to have originated via interspecific hybridization, although presumed sexual ancestors could only be identified in two cases. The allozyme and mtDNA data reveal the presence of many distinct clones within the presumed parthenogenetic lineages. This new instance of vertebrate parthenogenesis is a first for the Scincidae and only the second definitive case of unisexuality in an indigenous Australian vertebrate.

A Common Fold Mediates Vertebrate Defense and Bacterial Attack

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosado, Carlos J.; Buckle, Ashley M.; Law, Ruby H.P.

2008-10-02

Proteins containing membrane attack complex/perforin (MACPF) domains play important roles in vertebrate immunity, embryonic development, and neural-cell migration. In vertebrates, the ninth component of complement and perforin form oligomeric pores that lyse bacteria and kill virus-infected cells, respectively. However, the mechanism of MACPF function is unknown. We determined the crystal structure of a bacterial MACPF protein, Plu-MACPF from Photorhabdus luminescens, to 2.0 angstrom resolution. The MACPF domain reveals structural similarity with poreforming cholesterol-dependent cytolysins (CDCs) from Gram-positive bacteria. This suggests that lytic MACPF proteins may use a CDC-like mechanism to form pores and disrupt cell membranes. Sequence similarity between bacterialmore » and vertebrate MACPF domains suggests that the fold of the CDCs, a family of proteins important for bacterial pathogenesis, is probably used by vertebrates for defense against infection.« less

Ancient deuterostome origins of vertebrate brain signalling centres.

PubMed

Pani, Ariel M; Mullarkey, Erin E; Aronowicz, Jochanan; Assimacopoulos, Stavroula; Grove, Elizabeth A; Lowe, Christopher J

2012-03-14

Neuroectodermal signalling centres induce and pattern many novel vertebrate brain structures but are absent, or divergent, in invertebrate chordates. This has led to the idea that signalling-centre genetic programs were first assembled in stem vertebrates and potentially drove morphological innovations of the brain. However, this scenario presumes that extant cephalochordates accurately represent ancestral chordate characters, which has not been tested using close chordate outgroups. Here we report that genetic programs homologous to three vertebrate signalling centres-the anterior neural ridge, zona limitans intrathalamica and isthmic organizer-are present in the hemichordate Saccoglossus kowalevskii. Fgf8/17/18 (a single gene homologous to vertebrate Fgf8, Fgf17 and Fgf18), sfrp1/5, hh and wnt1 are expressed in vertebrate-like arrangements in hemichordate ectoderm, and homologous genetic mechanisms regulate ectodermal patterning in both animals. We propose that these genetic programs were components of an unexpectedly complex, ancient genetic regulatory scaffold for deuterostome body patterning that degenerated in amphioxus and ascidians, but was retained to pattern divergent structures in hemichordates and vertebrates. © 2012 Macmillan Publishers Limited. All rights reserved

Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain.

PubMed

Albuixech-Crespo, Beatriz; López-Blanch, Laura; Burguera, Demian; Maeso, Ignacio; Sánchez-Arrones, Luisa; Moreno-Bravo, Juan Antonio; Somorjai, Ildiko; Pascual-Anaya, Juan; Puelles, Eduardo; Bovolenta, Paola; Garcia-Fernàndez, Jordi; Puelles, Luis; Irimia, Manuel; Ferran, José Luis

2017-04-01

All vertebrate brains develop following a common Bauplan defined by anteroposterior (AP) and dorsoventral (DV) subdivisions, characterized by largely conserved differential expression of gene markers. However, it is still unclear how this Bauplan originated during evolution. We studied the relative expression of 48 genes with key roles in vertebrate neural patterning in a representative amphioxus embryonic stage. Unlike nonchordates, amphioxus develops its central nervous system (CNS) from a neural plate that is homologous to that of vertebrates, allowing direct topological comparisons. The resulting genoarchitectonic model revealed that the amphioxus incipient neural tube is unexpectedly complex, consisting of several AP and DV molecular partitions. Strikingly, comparison with vertebrates indicates that the vertebrate thalamus, pretectum, and midbrain domains jointly correspond to a single amphioxus region, which we termed Di-Mesencephalic primordium (DiMes). This suggests that these domains have a common developmental and evolutionary origin, as supported by functional experiments manipulating secondary organizers in zebrafish and mice.

Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain

PubMed Central

Albuixech-Crespo, Beatriz; Maeso, Ignacio; Sánchez-Arrones, Luisa; Moreno-Bravo, Juan Antonio; Somorjai, Ildiko; Pascual-Anaya, Juan; Puelles, Eduardo; Bovolenta, Paola; Garcia-Fernàndez, Jordi; Puelles, Luis; Ferran, José Luis

2017-01-01

All vertebrate brains develop following a common Bauplan defined by anteroposterior (AP) and dorsoventral (DV) subdivisions, characterized by largely conserved differential expression of gene markers. However, it is still unclear how this Bauplan originated during evolution. We studied the relative expression of 48 genes with key roles in vertebrate neural patterning in a representative amphioxus embryonic stage. Unlike nonchordates, amphioxus develops its central nervous system (CNS) from a neural plate that is homologous to that of vertebrates, allowing direct topological comparisons. The resulting genoarchitectonic model revealed that the amphioxus incipient neural tube is unexpectedly complex, consisting of several AP and DV molecular partitions. Strikingly, comparison with vertebrates indicates that the vertebrate thalamus, pretectum, and midbrain domains jointly correspond to a single amphioxus region, which we termed Di-Mesencephalic primordium (DiMes). This suggests that these domains have a common developmental and evolutionary origin, as supported by functional experiments manipulating secondary organizers in zebrafish and mice. PMID:28422959

STRIPAK complexes: structure, biological function, and involvement in human diseases.

PubMed

Hwang, Juyeon; Pallas, David C

2014-02-01

The mammalian striatin family consists of three proteins, striatin, S/G2 nuclear autoantigen, and zinedin. Striatin family members have no intrinsic catalytic activity, but rather function as scaffolding proteins. Remarkably, they organize multiple diverse, large signaling complexes that participate in a variety of cellular processes. Moreover, they appear to be regulatory/targeting subunits for the major eukaryotic serine/threonine protein phosphatase 2A. In addition, striatin family members associate with germinal center kinase III kinases as well as other novel components, earning these assemblies the name striatin-interacting phosphatase and kinase (STRIPAK) complexes. Recently, there has been a great increase in functional and mechanistic studies aimed at identifying and understanding the roles of STRIPAK and STRIPAK-like complexes in cellular processes of multiple organisms. These studies have identified novel STRIPAK and STRIPAK-like complexes and have explored their roles in specific signaling pathways. Together, the results of these studies have sparked increased interest in striatin family complexes because they have revealed roles in signaling, cell cycle control, apoptosis, vesicular trafficking, Golgi assembly, cell polarity, cell migration, neural and vascular development, and cardiac function. Moreover, STRIPAK complexes have been connected to clinical conditions, including cardiac disease, diabetes, autism, and cerebral cavernous malformation. In this review, we discuss the expression, localization, and protein domain structure of striatin family members. Then we consider the diverse complexes these proteins and their homologs form in various organisms, emphasizing what is known regarding function and regulation. Finally, we explore possible roles of striatin family complexes in disease, especially cerebral cavernous malformation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Regulation of asparagine-linked oligosaccharide processing. Oligosaccharide processing in Aedes albopictus mosquito cells.

PubMed

Hsieh, P; Robbins, P W

1984-02-25

We have examined the synthesis and processing of asparagine-linked oligosaccharides from Aedes albopictus C6/36 mosquito cells. These cells synthesized a glucose-containing lipid-linked oligosaccharide with properties identical to that of Glc3Man9GlcNAc2-PP-dolichol. Results of brief pulse label experiments with [3H]mannose were consistent with the transfer of Glc3Man9GlcNAc2 to protein followed by the rapid removal of glucose residues. Pulse-chase experiments established that further processing of oligosaccharides in C6/36 cells resulted in the removal of up to six alpha-linked mannose residues yielding Man3GlcNAc2 whose structure is identical to that of the trimannosyl "core" of N-linked oligosaccharides of vertebrate cells and yeast. Complex-type oligosaccharides were not observed in C6/36 cells. When Sindbis virus was grown in mosquito cells, Man3GlcNAc2 glycans were preferentially located at the two glycosylation sites which were previously shown to have complex glycans in virus grown in vertebrate cells. These Man3GlcNAc2 structures are the most extensively processed oligosaccharides in A. albopictus, and as such, are analogous to the complex glycans of vertebrate cells. We suggest that determinants of oligosaccharide processing which reside in the polypeptide are universally recognized despite evolutionary divergence of the oligosaccharide-processing pathway between insects and vertebrates.

Intraareolar polythelia: a rare anomaly.

PubMed

Köse, Rüstü; Ozgoönül, Abdullah; Bingöl, Ismet

2012-05-01

Polythelia, the presence of supernumerary nipples or nipple-areola complexes, is the most common anomaly of the pediatric breast. Although polythelia is common, intraareolar polythelia (nipple dichotomy) is an extremely rare congenital malformation. Surgical treatment is performed as a prophylaxis against breast cancer which has a higher prevalence in polythelia or polymastia. We describe a case of a young woman with polythelia in the right breast. The patient was a 25-year-old young woman who had two nipples by birth on the areola of the right breast. An abdominal ultrasound examination showed no urorenal malformations. Surgery was performed with elliptical excision under local anesthesia. A management of such cases with polythelia or polymastia was discussed in the view of recent literature.

Neonatal Death Dwarfism in a Girl with Distinctive Bone Dysplasia Compatible with Grebe Chondrodysplasia: Analysis by CT Scan-based Phenotype.

PubMed

Al Kaissi, Ali; Chehida, Farid Ben; Ganger, Rudolf; Grill, Franz

2014-01-01

We report on a female fetus noted to have severe malformative type of skeletal dysplasia on ultrasonography done at 35 weeks gestation. The girl died shortly after birth. Clinical examination showed a fetus with severe dwarfism, extensive long and short bones, and bone deficiencies associated with multiple dislocations. Computed tomography (CT) scan-based phenotype showed a complex constellation of malformations consistent with the diagnosis of Grebe syndrome. Parents being first cousins (consanguineous marriage) strongly suggests autosomal recessive pattern of inheritance. To our knowledge, this is the first report of neonatal death dwarfism of Grebe syndrome analyzed by CT scan-based phenotype.

[Dens invaginatus. Review of the literature and diagnostic and therapeutic guidelines].

PubMed

Baumgart, Manuela; Hänni, Stefan; Suter, Beat; Schaffner, Markus; Lussi, Adrian

2009-01-01

Dens invaginatus is a clinically relevant malformation of teeth resulting from an infolding of enamel and dentine into the dental structure during tooth formation, hence the former denomination "dens in dente". The dens invaginatus shows multiple morphological variations of crown and root formation. This frequently leads to caries, pulpal and periodontal involvement with necrosis and loss of attachment. Therefore, early diagnosis and prevention are of utmost importance. Due to the complexity of the malformation, treatment options in former days were limited. This article presents a profound review of the literature regarding etiology, epidemiology and histology. It discusses clinical appearance and diagnosis and it provides guidelines for decision-making and treatment of invaginated teeth.

Developmental outcomes of Down syndrome and Dandy-Walker malformation

PubMed Central

Love, Kaitlin; Huddleston, Lillie; Olney, Pat; Wrubel, David; Visootsak, Jeannie

2012-01-01

Dandy-Walker syndrome (DWS), or Dandy-Walker complex, is a congenital brain malformation of the posterior fossa, typically resulting in developmental delay and cognitive disability. The co-occurrence of Down syndrome (DS) and DWS is relatively uncommon; thus, its impact on developmental outcomes has not been fully elucidated. Herein, we report a case of a 37-month-old child with DS and DWS, who is functioning at the following age-equivalent: gross motor at a 9-mo level, fine motor 6 mo, expressive language 14 mo, receptive language 9 mo. As such, it is important to determine how the DWS influences developmental outcomes, and appreciate the importance of early interventional therapy. PMID:22866020

An approach to congenital malformations of the head and neck.

PubMed

Isaacson, Glenn

2007-02-01

It is easy to be overwhelmed when faced with the hundreds of cataloged anomalies of the head and neck region. For any individual defect there may be variation in phenotype, associated anomalies, and cause. To help organize these various disorders, dysmorphologists have grouped them into "syndromes", "sequences" and "associations" based on our level of understanding of their etiologies. Recently, completion of the human genome project has added a new level of complexity to the study of human malformations by providing a flood of new information about the genetic origins of established syndromes. The article describes the dysmorphologist's approach to the child with one or more anomalies and provides a glimpse into the future of human genetics.

Tissue specific roles for the ribosome biogenesis factor Wdr43 in zebrafish development.

PubMed

Zhao, Chengtian; Andreeva, Viktoria; Gibert, Yann; LaBonty, Melissa; Lattanzi, Victoria; Prabhudesai, Shubhangi; Zhou, Yi; Zon, Leonard; McCann, Kathleen L; Baserga, Susan; Yelick, Pamela C

2014-01-01

During vertebrate craniofacial development, neural crest cells (NCCs) contribute to most of the craniofacial pharyngeal skeleton. Defects in NCC specification, migration and differentiation resulting in malformations in the craniofacial complex are associated with human craniofacial disorders including Treacher-Collins Syndrome, caused by mutations in TCOF1. It has been hypothesized that perturbed ribosome biogenesis and resulting p53 mediated neuroepithelial apoptosis results in NCC hypoplasia in mouse Tcof1 mutants. However, the underlying mechanisms linking ribosome biogenesis and NCC development remain poorly understood. Here we report a new zebrafish mutant, fantome (fan), which harbors a point mutation and predicted premature stop codon in zebrafish wdr43, the ortholog to yeast UTP5. Although wdr43 mRNA is widely expressed during early zebrafish development, and its deficiency triggers early neural, eye, heart and pharyngeal arch defects, later defects appear fairly restricted to NCC derived craniofacial cartilages. Here we show that the C-terminus of Wdr43, which is absent in fan mutant protein, is both necessary and sufficient to mediate its nucleolar localization and protein interactions in metazoans. We demonstrate that Wdr43 functions in ribosome biogenesis, and that defects observed in fan mutants are mediated by a p53 dependent pathway. Finally, we show that proper localization of a variety of nucleolar proteins, including TCOF1, is dependent on that of WDR43. Together, our findings provide new insight into roles for Wdr43 in development, ribosome biogenesis, and also ribosomopathy-induced craniofacial phenotypes including Treacher-Collins Syndrome.

Temporal bone changes in patients with Goldenhar syndrome with special emphasis on inner ear abnormalities.

PubMed

Hennersdorf, Florian; Friese, Natascha; Löwenheim, Hubert; Tropitzsch, Anke; Ernemann, Ulrike; Bisdas, Sotirios

2014-06-01

Goldenhar syndrome is a developmental disorder presenting with orofacial and vertebral anomalies, which are also accompanied by abnormalities in other organs. We examined temporal bone changes with special emphasis on inner ear abnormalities in these patients. A retrospective review of 7 new cases in addition to a previously published series of 14 cases with clinically diagnosed Goldenhar syndrome was carried out to search for inner ear anomalies. In addition, temporal bone imaging studies from the literature were summarized and compared with our results. Departments of Neuroradiology and Otorhinolaryngology at a university hospital. In addition to the previous series of 14 patients, 7 new patients with Goldenhar syndrome were identified. Patients underwent otologic examination, audiometric studies, and high-resolution computed tomography (CT) or magnetic resonance imaging (MRI) of the temporal bone. Temporal bone changes and specifically inner ear malformations. Nineteen of 21 patients showed changes of the external and middle ear correlating with the literature. Seven of 21 patients showed inner ear abnormalities constituting one-third of all patients. These ranged from mild such as vestibular enlargement to severe defects such as cochlear hypoplasia and common cavity. Inner ear abnormalities were present in one-third of patients. Although in some cases, these might not be of clinical significance, some patients show severe defects of the inner ear requiring more complex hearing loss therapy. Therefore, imaging of the temporal bone structures is important in the care of these patients.

Video Views and Reviews: Neurulation and the Fashioning of the Vertebrate Central Nervous System

ERIC Educational Resources Information Center

Watters, Christopher

2006-01-01

The central nervous system (CNS) is the first adult organ system to appear during vertebrate development, and the process of its emergence is commonly called neurulation. Such biological "urgency" is perhaps not surprising given the structural and functional complexity of the CNS and the importance of neural function to adaptive behavior and…

Intake of high levels of vitamin A and polyunsaturated fatty acids during different developmental periods modifies the expression of morphogenesis genes in European sea bass (Dicentrarchus labrax).

PubMed

Villeneuve, Laure A N; Gisbert, Enric; Moriceau, Jacques; Cahu, Chantal L; Zambonino Infante, José L

2006-04-01

The effect of the feeding period on larval development was investigated in European sea bass larvae by considering the expression level of some genes involved in morphogenesis. Larvae were fed a control diet except during three different periods (period A: from 8 to 13 d post-hatching (dph); period B: from 13 to 18 dph; period C: from 18 to 23 dph) with two compound diets containing high levels of vitamin A or PUFA. European sea bass morphogenesis was affected by these two dietary nutrients during the early stages of development. The genes involved in morphogenesis could be modulated between 8 and 13 dph, and our results indicated that retinoids and fatty acids influenced two different molecular pathways that in turn implicated two different gene cascades, resulting in two different kinds of malformation. Hypervitaminosis A delayed development, reducing the number of vertebral segments and disturbing bone formation in the cephalic region. These malformations were correlated to an upregulation of retinoic acid receptor gamma, retinoid X receptor (RXR) alpha and bone morphogenetic protein (BMP)4. An excess of PUFA accelerated the osteoblast differentiation process through the upregulation of RXRalpha and BMP4, leading to a supernumerary vertebra. These results suggest that the composition of diets devoted to marine fish larvae has a particularly determining effect before 13 dph on the subsequent development of larvae and juvenile fish.

Developmental evolutionary biology of the vertebrate ear: conserving mechanoelectric transduction and developmental pathways in diverging morphologies

NASA Technical Reports Server (NTRS)

Fritzsch, B.; Beisel, K. W.; Bermingham, N. A.

2000-01-01

This brief overview shows that a start has been made to molecularly dissect vertebrate ear development and its evolutionary conservation to the development of the insect hearing organ. However, neither the patterning process of the ear nor the patterning process of insect sensory organs is sufficiently known at the moment to provide more than a first glimpse. Moreover, hardly anything is known about otocyst development of the cephalopod molluscs, another triploblast lineage that evolved complex 'ears'. We hope that the apparent conserved functional and cellular components present in the ciliated sensory neurons/hair cells will also be found in the genes required for vertebrate ear and insect sensory organ morphogenesis (Fig. 3). Likewise, we expect that homologous pre-patterning genes will soon be identified for the non-sensory cell development, which is more than a blocking of neuronal development through the Delta/Notch signaling system. Generation of the apparently unique ear could thus represent a multiplication of non-sensory cells by asymmetric and symmetric divisions as well as modification of existing patterning process by implementing novel developmental modules. In the final analysis, the vertebrate ear may come about by increasing the level of gene interactions in an already existing and highly conserved interactive cascade of bHLH genes. Since this was apparently achieved in all three lineages of triploblasts independently (Fig. 3), we now need to understand how much of the morphogenetic cascades are equally conserved across phyla to generate complex ears. The existing mutations in humans and mice may be able to point the direction of future research to understand the development of specific cell types and morphologies in the formation of complex arthropod, cephalopod, and vertebrate 'ears'.

The Role of Cerl2 in the Establishment of Left-Right Asymmetries during Axis Formation and Heart Development

PubMed Central

2017-01-01

The formation of the asymmetric left-right (LR) body axis is one of the fundamental aspects of vertebrate embryonic development, and one still raising passionate discussions among scientists. Although the conserved role of nodal is unquestionable in this process, several of the details around this signaling cascade are still unanswered. To further understand this mechanism, we have been studying Cerberus-like 2 (Cerl2), an inhibitor of Nodal, and its role in the generation of asymmetries in the early vertebrate embryo. The absence of Cerl2 results in a wide spectrum of malformations commonly known as heterotaxia, which comprises defects in either global organ position (e.g., situs inversus totalis), reversed orientation of at least one organ (e.g., situs ambiguus), and mirror images of usually asymmetric paired organs (e.g., left or right isomerisms of the lungs). Moreover, these laterality defects are frequently associated with congenital heart diseases (e.g., transposition of the great arteries, or atrioventricular septal defects). Here, reviewing the knowledge on the establishment of LR asymmetry in mouse embryos, the emerging conclusion is that as necessary as is the activation of the Nodal signaling cascade, the tight control that Cerl2-mediates on Nodal signaling is equally important, and that generates a further regionalized LR genetic program in the proper time and space. PMID:29367552

Subclavian Steal Syndrome with or without Arterial Stenosis: A Review.

PubMed

Kargiotis, Odysseas; Siahos, Simos; Safouris, Apostolos; Feleskouras, Agisilaos; Magoufis, Georgios; Tsivgoulis, Georgios

2016-09-01

The subclavian-vertebral artery steal syndrome (SSS) is the hemodynamic phenomenon of blood flow reversal in the vertebral artery due to significant stenosis or occlusion of the proximal subclavian artery or the innominate artery. Occasionally, SSS is diagnosed in patients not harboring arterial stenosis. With the exception of arterial congenital malformations, the limited case reports of SSS with intact subclavian artery are attributed to dialysis arteriovenous fistulas (AVFs). Interestingly, these cases are more frequently symptomatic than those with the classical atherosclerotic SSS forms. On the other hand, the disclosure of SSS due to subclavian/innominate artery atherosclerotic stenosis, even in the absence of accompanying symptoms, should prompt a thorough cardiovascular work-up for the early detection of coexisting coronary, carotid, or peripheral artery disease. Herein, we review the incidence, clinical presentation, sonographic findings, and therapeutic interventions related to SSS with and without subclavian/innominate artery stenosis. We also review the currently available data in the literature regarding the association of SSS and dialysis AVF. In addition, we present a patient with bilateral symptomatic SSS as the result of an arteriovenous graft (AVG) that was introduced after the preexisting AVF in the contralateral arm became nonfunctional. SSS due to subclavian or innominate artery stenosis/occlusion is rarely symptomatic warranting interventional treatment. In contrast, when it is attributed to AVF, surgical correction is frequently necessary. Copyright © 2016 by the American Society of Neuroimaging.

Intraflagellar transport genes are essential for differentiation and survival of vertebrate sensory neurons.

PubMed

Tsujikawa, Motokazu; Malicki, Jarema

2004-06-10

Cilia play diverse roles in vertebrate and invertebrate sensory neurons. We show that a mutation of the zebrafish oval (ovl) locus affects a component of the ciliary transport (IFT) mechanism, the IFT88 polypeptide. In mutant retina, cilia are generated but not maintained, producing the absence of photoreceptor outer segments. A loss of cilia also occurs in auditory hair cells and olfactory sensory neurons. In all three sense organs, cilia defects are followed by degeneration of sensory cells. Similar phenotypes are induced by the absence of the IFT complex B polypeptides, ift52 and ift57, but not by the loss of complex A protein, ift140. The degeneration of mutant photoreceptor cells is caused, at least partially, by the ectopic accumulation of opsins. These studies reveal an essential role for IFT genes in vertebrate sensory neurons and implicate the molecular components of intraflagellar transport in degenerative disorders of these cells.

What can fish brains tell us about visual perception?

PubMed Central

Rosa Salva, Orsola; Sovrano, Valeria Anna; Vallortigara, Giorgio

2014-01-01

Fish are a complex taxonomic group, whose diversity and distance from other vertebrates well suits the comparative investigation of brain and behavior: in fish species we observe substantial differences with respect to the telencephalic organization of other vertebrates and an astonishing variety in the development and complexity of pallial structures. We will concentrate on the contribution of research on fish behavioral biology for the understanding of the evolution of the visual system. We shall review evidence concerning perceptual effects that reflect fundamental principles of the visual system functioning, highlighting the similarities and differences between distant fish groups and with other vertebrates. We will focus on perceptual effects reflecting some of the main tasks that the visual system must attain. In particular, we will deal with subjective contours and optical illusions, invariance effects, second order motion and biological motion and, finally, perceptual binding of object properties in a unified higher level representation. PMID:25324728

The buccohypophyseal canal is an ancestral vertebrate trait maintained by modulation in sonic hedgehog signaling

PubMed Central

2013-01-01

Background The pituitary gland is formed by the juxtaposition of two tissues: neuroectoderm arising from the basal diencephalon, and oral epithelium, which invaginates towards the central nervous system from the roof of the mouth. The oral invagination that reaches the brain from the mouth is referred to as Rathke’s pouch, with the tip forming the adenohypophysis and the stalk disappearing after the earliest stages of development. In tetrapods, formation of the cranial base establishes a definitive barrier between the pituitary and oral cavity; however, numerous extinct and extant vertebrate species retain an open buccohypophyseal canal in adulthood, a vestige of the stalk of Rathke’s pouch. Little is currently known about the formation and function of this structure. Here we have investigated molecular mechanisms driving the formation of the buccohypophyseal canal and their evolutionary significance. Results We show that Rathke’s pouch is located at a boundary region delineated by endoderm, neural crest-derived oral mesenchyme and the anterior limit of the notochord, using CD1, R26R-Sox17-Cre and R26R-Wnt1-Cre mouse lines. As revealed by synchrotron X-ray microtomography after iodine staining in mouse embryos, the pouch has a lobulated three-dimensional structure that embraces the descending diencephalon during pituitary formation. Polarisfl/fl; Wnt1-Cre, Ofd1-/- and Kif3a-/- primary cilia mouse mutants have abnormal sonic hedgehog (Shh) signaling and all present with malformations of the anterior pituitary gland and midline structures of the anterior cranial base. Changes in the expressions of Shh downstream genes are confirmed in Gas1-/- mice. From an evolutionary perspective, persistence of the buccohypophyseal canal is a basal character for all vertebrates and its maintenance in several groups is related to a specific morphology of the midline that can be related to modulation in Shh signaling. Conclusion These results provide insight into a poorly understood ancestral vertebrate structure. It appears that the opening of the buccohypophyseal canal depends upon Shh signaling and that modulation in this pathway most probably accounts for its persistence in phylogeny. PMID:23537390

C7 vertebra homeotic transformation in domestic dogs - are Pug dogs breaking mammalian evolutionary constraints?

PubMed

Brocal, J; De Decker, S; José-López, R; Manzanilla, E G; Penderis, J; Stalin, C; Bertram, S; Schoenebeck, J J; Rusbridge, C; Fitzpatrick, N; Gutierrez-Quintana, R

2018-05-14

The number of cervical vertebrae in mammals is almost constant at seven, regardless of their neck length, implying that there is selection against variation in this number. Homebox (Hox) genes are involved in this evolutionary mammalian conservation, and homeotic transformation of cervical into thoracic vertebrae (cervical ribs) is a common phenotypic abnormality when Hox gene expression is altered. This relatively benign phenotypic change can be associated with fatal traits in humans. Mutations in genes upstream of Hox, inbreeding and stressors during organogenesis can also cause cervical ribs. The aim of this study was to describe the prevalence of cervical ribs in a large group of domestic dogs of different breeds, and explore a possible relation with other congenital vertebral malformations (CVMs) in the breed with the highest prevalence of cervical ribs. By phenotyping we hoped to give clues as to the underlying genetic causes. Twenty computed tomography studies from at least two breeds belonging to each of the nine groups recognized by the Federation Cynologique Internationale, including all the brachycephalic 'screw-tailed' breeds that are known to be overrepresented for CVMs, were reviewed. The Pug dog was more affected by cervical ribs than any other breed (46%; P < 0.001), and was selected for further analysis. No association was found between the presence of cervical ribs and vertebral body formation defect, bifid spinous process, caudal articular process hypoplasia/aplasia and an abnormal sacrum, which may infer they have a different aetiopathogenesis. However, Pug dogs with cervical ribs were more likely to have a transitional thoraco-lumbar vertebra (P = 0.041) and a pre-sacral vertebral count of 26 (P < 0.001). Higher C7/T1 dorsal spinous processes ratios were associated with the presence of cervical ribs (P < 0.001), supporting this is a true homeotic transformation. Relaxation of the stabilizing selection has likely occurred, and the Pug dog appears to be a good naturally occurring model to further investigate the aetiology of cervical ribs, other congenital vertebral anomalies and numerical alterations. © 2018 Anatomical Society.

The buccohypophyseal canal is an ancestral vertebrate trait maintained by modulation in sonic hedgehog signaling.

PubMed

Khonsari, Roman H; Seppala, Maisa; Pradel, Alan; Dutel, Hugo; Clément, Gaël; Lebedev, Oleg; Ghafoor, Sarah; Rothova, Michaela; Tucker, Abigael; Maisey, John G; Fan, Chen-Ming; Kawasaki, Maiko; Ohazama, Atsushi; Tafforeau, Paul; Franco, Brunella; Helms, Jill; Haycraft, Courtney J; David, Albert; Janvier, Philippe; Cobourne, Martyn T; Sharpe, Paul T

2013-03-28

The pituitary gland is formed by the juxtaposition of two tissues: neuroectoderm arising from the basal diencephalon, and oral epithelium, which invaginates towards the central nervous system from the roof of the mouth. The oral invagination that reaches the brain from the mouth is referred to as Rathke's pouch, with the tip forming the adenohypophysis and the stalk disappearing after the earliest stages of development. In tetrapods, formation of the cranial base establishes a definitive barrier between the pituitary and oral cavity; however, numerous extinct and extant vertebrate species retain an open buccohypophyseal canal in adulthood, a vestige of the stalk of Rathke's pouch. Little is currently known about the formation and function of this structure. Here we have investigated molecular mechanisms driving the formation of the buccohypophyseal canal and their evolutionary significance. We show that Rathke's pouch is located at a boundary region delineated by endoderm, neural crest-derived oral mesenchyme and the anterior limit of the notochord, using CD1, R26R-Sox17-Cre and R26R-Wnt1-Cre mouse lines. As revealed by synchrotron X-ray microtomography after iodine staining in mouse embryos, the pouch has a lobulated three-dimensional structure that embraces the descending diencephalon during pituitary formation. Polaris(fl/fl); Wnt1-Cre, Ofd1(-/-) and Kif3a(-/-) primary cilia mouse mutants have abnormal sonic hedgehog (Shh) signaling and all present with malformations of the anterior pituitary gland and midline structures of the anterior cranial base. Changes in the expressions of Shh downstream genes are confirmed in Gas1(-/-) mice. From an evolutionary perspective, persistence of the buccohypophyseal canal is a basal character for all vertebrates and its maintenance in several groups is related to a specific morphology of the midline that can be related to modulation in Shh signaling. These results provide insight into a poorly understood ancestral vertebrate structure. It appears that the opening of the buccohypophyseal canal depends upon Shh signaling and that modulation in this pathway most probably accounts for its persistence in phylogeny.

A Case of Vaginal Stillbirth in the Presence of Placenta Previa at 33 Weeks of Gestation

PubMed Central

Chinen, Yukiko; Kinjo, Tadatsugu; Nitta, Hayase; Kinjo, Yui; Masamoto, Hitoshi

2016-01-01

It was demonstrated that second- and third-trimester therapeutic termination of pregnancy (TOP) is feasible in cases with placenta previa. We report a 34-year-old woman with complex fetal malformations associated with placenta previa. An ultrasound examination at 21 weeks of gestation revealed fetal growth restriction (FGR) and complex fetal malformations associated with a placenta previa. After extensive information, the parents opted for careful observation. Thereafter, FGR gradually progressed and we observed arrest of end-diastolic velocity of the umbilical artery. Finally, intrauterine fetal death (IUFD) was confirmed at 33 weeks of gestation. Two days after IUFD, the patient experienced labor pain. The placenta and dead fetus weighing 961 g were vaginally delivered, and total bleeding was 270 mL. Although further studies to confirm the dynamic change of the uteroplacental blood flow are necessary to avoid the risk of maternal hemorrhage, vaginal TOP with placenta previa after feticide or IUFD would be feasible. PMID:27579202

Pulmonary hypoplasia in Jarcho-Levin syndrome.

PubMed

Rodríguez, Luis M; García-García, Inés; Correa-Rivas, María S; García-Fragoso, Lourdes

2004-03-01

Jarcho-Levin syndrome, also known as spondylothoracic dysplasia and characterized by short trunk dwarfism, "crab-like" rib cage, with ribs and vertebral defects; it is not uncommon in Puerto Ricans. Many patients die in early infancy due to respiratory compromise associated to lung restriction and the reported cases emphasize mostly the skeletal malformations associated to the syndrome. We report the autopsy findings in a newborn with isolated Jarcho-Levin syndrome emphasizing pulmonary pathology. He was a pre-term male who died of respiratory failure at three hours old and, autopsy findings confirmed the clinical diagnosis. Internal examination showed hypoplastic lungs with normal lobation. The histological structure appeared normal and relatively mature; the diaphragm showed eventration and unilateral absence of musculature. This case shows the worst spectum of the Jarcho-Levin syndrome: pulmonary hypoplasia not compatible with extrauterine life. Since thoracic restriction is present during the fetal period, the degree of pulmonary hypoplasia probably defines survival beyond the neonatal period.

Compressive myelopathy of the cervical spine in Komodo dragons (Varanus komodoensis).

PubMed

Zimmerman, Dawn M; Douglass, Michael; Sutherland-Smith, Meg; Aguilar, Roberto; Schaftenaar, Willem; Shores, Andy

2009-03-01

Cervical subluxation and compressive myelopathy appears to be a cause of morbidity and mortality in captive Komodo dragons (Varanus komodoensis). Four cases of cervical subluxation resulting in nerve root compression or spinal cord compression were identified. Three were presumptively induced by trauma, and one had an unknown inciting cause. Two dragons exhibited signs of chronic instability. Cervical vertebrae affected included C1-C4. Clinical signs on presentation included ataxia, ambulatory paraparesis or tetraparesis to tetraplegia, depression to stupor, cervical scoliosis, and anorexia. Antemortem diagnosis of compression was only confirmed with magnetic resonance imaging or computed tomography. Treatment ranged from supportive care to attempted surgical decompression. All dragons died or were euthanatized, at 4 days to 12 mo postpresentation. Studies to define normal vertebral anatomy in the species are necessary to determine whether the pathology is linked to cervical malformation, resulting in ligament laxity, subsequent instability, and subluxation.

Effects of audiogenic hazard on fetal skeletal development in mice

NASA Astrophysics Data System (ADS)

Murata, M.; Kawade, F.; Kondo, M.; Takigawa, H.; Sakamoto, H.

1990-06-01

The effects of noise on fetal skeletal development in mice were examined. Pregnant ICR mice were exposed to a wide octave-band noise at 100 dB(C) for 6 hours a day in three ways: the first group was continuously exposed only on day 7 of pregnancy (group "N"); the second was exposed intermittently (15 min on/15 min off) only on day 7 of pregnancy (group "IN"); and the third was exposed to a continuous noise recurrently during days 7-12 of pregnancy (group "RN"). On day 18 of pregnancy, fetuses were removed and prepared as skeletons of cleared specimens stained with alizarin red S for examining skeletal development. Skeletal immaturity was observed in group "RN". The percentage of fetuses with skeletal malformations was significantly increased in group "N", as compared with the control. Significantly higher percentages of fetuses with variations in cervical vertebral arches were observed in groups "N" and "RN".

Response to Lefebvre et al.

PubMed

Takeda, K; Kou, I; Kawakami, N; Yasuhiko, Y; Ogura, Y; Imagawa, E; Miyake, N; Matsumoto, N; Sudo, H; Kotani, T; Nakamura, M; Matsumoto, M; Watanabe, K; Ikegawa, S

2017-11-01

Congenital scoliosis (CS) is a common vertebral malformation with incidence of up to 1 of 1000 births worldwide. Recently, TBX6 has been reported as the first disease gene for CS: about 10% of CS patients are compound heterozygotes of rare null mutations and a common haplotype composed by 3 SNPs in TBX6. Lefebvre et al in this journal reported that 2 patients with spondylocostal dysostosis (SCD), a rare skeletal dysplasia affecting spine and ribs also have TBX6 mutations: 1 carried the microdeletion and a rare missense variant, and another 2 rare missense variants. We investigated the pathogenicity of the 3 missense variants in SCD by a luciferase assay. The results were negative for the proposal of Lefebvre et al. We consider these 2 SCD patients are more probably compound heterozygotes of null mutations and a common risk haplotype just as CS patients with TBX6 mutations. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Polydactyly in Development, Inheritance, and Evolution.

PubMed

Lange, Axel; Müller, Gerd B

2017-03-01

The occurrence of supernumerary digits or toes in humans and other tetrapods has attracted general interest since antiquity and later influenced scientific theories of development, inheritance, and evolution. Seventeenth-century genealogical studies of polydactyly were at the beginning of an understanding of the rules of inheritance. Features of polydactyly were also part of the classical disputes on the nature of development, including the preformation-versus-epigenesis and the atavism-versus-malformation debates. In the evolutionary domain, polydactyly was used in the criticism of the gradualist account of variation underlying Darwin’s theory. Today, extra digit formation plays a role in the conceptualization of gene regulation and pattern formation in vertebrate limb evolution. Recent genetic, experimental, and modeling accounts of extra digit formation highlight the existence of nongradual transitions in phenotypic states, suggesting a distinction between continuous and discontinuous variation in evolution. Unless otherwise noted, all translations are our own.

Phylostratigraphic profiles reveal a deep evolutionary history of the vertebrate head sensory systems

PubMed Central

2013-01-01

Background The vertebrate head is a highly derived trait with a heavy concentration of sophisticated sensory organs that allow complex behaviour in this lineage. The head sensory structures arise during vertebrate development from cranial placodes and the neural crest. It is generally thought that derivatives of these ectodermal embryonic tissues played a central role in the evolutionary transition at the onset of vertebrates. Despite the obvious importance of head sensory organs for vertebrate biology, their evolutionary history is still uncertain. Results To give a fresh perspective on the adaptive history of the vertebrate head sensory organs, we applied genomic phylostratigraphy to large-scale in situ expression data of the developing zebrafish Danio rerio. Contrary to traditional predictions, we found that dominant adaptive signals in the analyzed sensory structures largely precede the evolutionary advent of vertebrates. The leading adaptive signals at the bilaterian-chordate transition suggested that the visual system was the first sensory structure to evolve. The olfactory, vestibuloauditory, and lateral line sensory organs displayed a strong link with the urochordate-vertebrate ancestor. The only structures that qualified as genuine vertebrate innovations were the neural crest derivatives, trigeminal ganglion and adenohypophysis. We also found evidence that the cranial placodes evolved before the neural crest despite their proposed embryological relatedness. Conclusions Taken together, our findings reveal pre-vertebrate roots and a stepwise adaptive history of the vertebrate sensory systems. This study also underscores that large genomic and expression datasets are rich sources of macroevolutionary information that can be recovered by phylostratigraphic mining. PMID:23587066

Brain architecture and social complexity in modern and ancient birds.

PubMed

Burish, Mark J; Kueh, Hao Yuan; Wang, Samuel S-H

2004-01-01

Vertebrate brains vary tremendously in size, but differences in form are more subtle. To bring out functional contrasts that are independent of absolute size, we have normalized brain component sizes to whole brain volume. The set of such volume fractions is the cerebrotype of a species. Using this approach in mammals we previously identified specific associations between cerebrotype and behavioral specializations. Among primates, cerebrotypes are linked principally to enlargement of the cerebral cortex and are associated with increases in the complexity of social structure. Here we extend this analysis to include a second major vertebrate group, the birds. In birds the telencephalic volume fraction is strongly correlated with social complexity. This correlation accounts for almost half of the observed variation in telencephalic size, more than any other behavioral specialization examined, including the ability to learn song. A prominent exception to this pattern is owls, which are not social but still have very large forebrains. Interpolating the overall correlation for Archaeopteryx, an ancient bird, suggests that its social complexity was likely to have been on a par with modern domesticated chickens. Telencephalic volume fraction outperforms residuals-based measures of brain size at separating birds by social structure. Telencephalic volume fraction may be an anatomical substrate for social complexity, and perhaps cognitive ability, that can be generalized across a range of vertebrate brains, including dinosaurs. Copyright 2004 S. Karger AG, Basel

Anomalous Origin of the Right Vertebral Artery: Incidence and Significance.

PubMed

Maiti, Tanmoy Kumar; Konar, Subhas Kanti; Bir, Shyamal; Nanda, Anil; Cuellar, Hugo

2016-05-01

Detailed knowledge about anatomic variations of the aortic arch and its multiple branches is extremely important to endovascular and diagnostic radiologists. It is often hypothesized that anomalous origin and distribution of large aortic vessels may alter the cerebral hemodynamics and potentially lead to a vascular pathology. In this article, we describe a case of anomalous origin of the right vertebral artery, which was detected during an intervention. We further reviewed the available literature of anomalous origin of the right vertebral artery. The probable embryologic development and clinical significance are discussed. The incidence of anomalous origin of a vertebral artery seems to be underestimated in recent literature. A careful review of the literature shows more than 100 such cases. The right vertebral artery can arise from the aortic arch or one of its branches. Dual origin of the vertebral artery is not uncommon. The embryologic developmental hypotheses are contradictory and complex. Anomalous origin of the right vertebral artery may not be the sole reason behind a disease process. However, it can certainly lead to a misdiagnosis during diagnostic vascular studies. Detailed information is essential for any surgery or endovascular intervention in this location. Copyright © 2015 Elsevier Inc. All rights reserved.

Dlx5 Homeodomain: DNA Complex: Structure, Binding and Effect of Mutations Related to Split Hand and Foot Malformation Syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Proudfoot, Andrew; Axelrod, Herbert L.; Geralt, Michael

The Dlx5 homeodomain is a transcription factor related to the Drosophila Distal-less gene that is associated with breast and lung cancer, lymphoma, Rett syndrome and osteoporosis in humans. Mutations in the DLX5 gene have been linked to deficiencies in craniofacial and limb development in higher eukaryotes, including Split Hand and Foot Malformation-1 (SHFM-1) in humans. Our characterization of a Dlx5 homeodomain–(CGACTAATTAGTCG) 2 complex by NMR spectroscopy paved the way for determination of its crystal structure at 1.85 Å resolution that enabled rationalization of the effects of disease-related mutations on the protein function. A remarkably subtle mutation, Q186H, is linked tomore » SHFM-1; this change likely affects affinity of DNA binding by disrupting water-mediated interactions with the DNA major groove. A more subtle effect is implicated for the Q178P mutation, which is not in direct contact with the DNA. Our data indicate that these mutations diminish the ability of the Dlx5 homeodomain to recognize and bind target DNAs, and likely destabilize the formation of functional complexes.« less

Dlx5 Homeodomain: DNA Complex: Structure, Binding and Effect of Mutations Related to Split Hand and Foot Malformation Syndrome

DOE PAGES

Proudfoot, Andrew; Axelrod, Herbert L.; Geralt, Michael; ...

2016-01-29

The Dlx5 homeodomain is a transcription factor related to the Drosophila Distal-less gene that is associated with breast and lung cancer, lymphoma, Rett syndrome and osteoporosis in humans. Mutations in the DLX5 gene have been linked to deficiencies in craniofacial and limb development in higher eukaryotes, including Split Hand and Foot Malformation-1 (SHFM-1) in humans. Our characterization of a Dlx5 homeodomain–(CGACTAATTAGTCG) 2 complex by NMR spectroscopy paved the way for determination of its crystal structure at 1.85 Å resolution that enabled rationalization of the effects of disease-related mutations on the protein function. A remarkably subtle mutation, Q186H, is linked tomore » SHFM-1; this change likely affects affinity of DNA binding by disrupting water-mediated interactions with the DNA major groove. A more subtle effect is implicated for the Q178P mutation, which is not in direct contact with the DNA. Our data indicate that these mutations diminish the ability of the Dlx5 homeodomain to recognize and bind target DNAs, and likely destabilize the formation of functional complexes.« less

Phylogenetic investigation of human FGFR-bearing paralogons favors piecemeal duplication theory of vertebrate genome evolution.

PubMed

Ajmal, Wajya; Khan, Hiba; Abbasi, Amir Ali

2014-12-01

Understanding the genetic mechanisms underlying the organismal complexity and origin of novelties during vertebrate history is one of the central goals of evolutionary biology. Ohno (1970) was the first to postulate that whole genome duplications (WGD) have played a vital role in the evolution of new gene functions: permitting an increase in morphological, physiological and anatomical complexity during early vertebrate history. Here, we analyze the evolutionary history of human FGFR-bearing paralogon (human autosome 4/5/8/10) by the phylogenetic analysis of multigene families with triplicate and quadruplicate distribution on these chromosomes. Our results categorized the histories of 21 families into discrete co-duplicated groups. Genes of a particular co-duplicated group exhibit identical evolutionary history and have duplicated in concert with each other, whereas genes belonging to different groups have dissimilar histories and have not duplicated concurrently. Taken together with our previously published data, we submit that there is sufficient empirical evidence to disprove the 1R/2R hypothesis and to support the general prediction that vertebrate genome evolved by relatively small-scale, regional duplication events that spread across the history of life. Copyright © 2014 Elsevier Inc. All rights reserved.

Dosimetric quality, accuracy, and deliverability of modulated radiotherapy treatments for spinal metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kairn, Tanya, E-mail: t.kairn@gmail.com; School of Chemistry, Physics, and Mechanical Engineering, Queensland University of Technology, Brisbane; Papworth, Daniel

2016-10-01

Cancer often metastasizes to the vertebra, and such metastases can be treated successfully using simple, static posterior or opposed-pair radiation fields. However, in some cases, including when re-irradiation is required, spinal cord avoidance becomes necessary and more complex treatment plans must be used. This study evaluated 16 sample intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) treatment plans designed to treat 6 typical vertebral and paraspinal volumes using a standard prescription, with the aim of investigating the advantages and limitations of these treatment techniques and providing recommendations for their optimal use in vertebral treatments. Treatment plan quality and beammore » complexity metrics were evaluated using the Treatment And Dose Assessor (TADA) code. A portal-imaging–based quality assurance (QA) system was used to evaluate treatment delivery accuracy, and radiochromic film measurements were used to provide high-resolution verification of treatment plan dose accuracy, especially in the steep dose gradient regions between each vertebral target and spinal cord. All treatment modalities delivered approximately the same doses and the same levels of dose heterogeneity to each planning target volume (PTV), although the minimum PTV doses in the vertebral plans were substantially lower than the prescription, because of the requirement that the plans meet a strict constraint on the dose to the spinal cord and cord planning risk volume (PRV). All plans met required dose constraints on all organs at risk, and all measured PTV-cord dose gradients were steeper than planned. Beam complexity analysis suggested that the IMRT treatment plans were more deliverable (less complex, leading to greater QA success) than the VMAT treatment plans, although the IMRT plans also took more time to deliver. The accuracy and deliverability of VMAT treatment plans were found to be substantially increased by limiting the number of monitor units (MU) per beam at the optimization stage, and thereby limiting beam modulation complexity. The VMAT arcs that were optimized with MU limitation had higher QA pass rates as well as higher modulation complexity scores (less complexity), lower modulation indices (less modulation), lower MU per beam, larger beam segments, and fewer small apertures than the VMAT arcs that were optimized without MU limitation. It is recommended that VMAT treatments for vertebral volumes, where the PTV abuts or surrounds the spinal cord, should be optimized with MU limitation. IMRT treatments may be preferable to the VMAT treatments, for dosimetry and deliverability reasons, but may be inappropriate for some patients because of their increased treatment delivery time.« less

75 FR 41501 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-16

..., mental retardation or learning disabilities, and behavioral problems, as well as malformations in many... degree of mental retardation and learning disability. Biochemically, SLOS is caused by disruption of the..., but the mechanism of resistance is highly complex; this mouse model will be useful in learning the...

Anomalies of the systemic venous return: a review.

PubMed

Mazzucco, A; Bortolotti, U; Stellin, G; Gallucci, V

1990-06-01

Congenital anomalies of the systemic venous connection to the heart represent a rather wide and heterogeneous group of malformations, whose physiological consequences may vary from nil to the most severe form of systemic arterial desaturation. The malformations may be summarized as follows: (1) Left superior vena cava connected to the coronary sinus, interrupted inferior vena cava and absent right superior vena cava that do not indicate surgical repair 'per se', but require some technical attention during open heart surgery performed for other anomalies; (2) Left superior vena cava connected to the left atrium, due to incorporation of the coronary sinus into the left atrial cavity, resulting in a right-to-left-shunt; (3) Right superior vena cava or inferior vena cava draining into the left atrium, both are extremely rare and require treatment for the ensuing right-to-left shunt; (4) Total anomalous systemic venous connection to the left atrium, usually combined with atrial isomerism and other very complex heart malformations; (5) Cor triatriatum dexter, which has been frequently diagnosed as an anomalous venous connection for its similar hemodynamic consequences. Such anomalies are reviewed with particular respect to their surgical implications.

RING1 is associated with the polycomb group protein complex and acts as a transcriptional repressor.

PubMed

Satijn, D P; Gunster, M J; van der Vlag, J; Hamer, K M; Schul, W; Alkema, M J; Saurin, A J; Freemont, P S; van Driel, R; Otte, A P

1997-07-01

The Polycomb (Pc) protein is a component of a multimeric, chromatin-associated Polycomb group (PcG) protein complex, which is involved in stable repression of gene activity. The identities of components of the PcG protein complex are largely unknown. In a two-hybrid screen with a vertebrate Pc homolog as a target, we identify the human RING1 protein as interacting with Pc. RING1 is a protein that contains the RING finger motif, a specific zinc-binding domain, which is found in many regulatory proteins. So far, the function of the RING1 protein has remained enigmatic. Here, we show that RING1 coimmunoprecipitates with a human Pc homolog, the vertebrate PcG protein BMI1, and HPH1, a human homolog of the PcG protein Polyhomeotic (Ph). Also, RING1 colocalizes with these vertebrate PcG proteins in nuclear domains of SW480 human colorectal adenocarcinoma and Saos-2 human osteosarcoma cells. Finally, we show that RING1, like Pc, is able to repress gene activity when targeted to a reporter gene. Our findings indicate that RING1 is associated with the human PcG protein complex and that RING1, like PcG proteins, can act as a transcriptional repressor.

Common developmental pathways link tooth shape to regeneration

PubMed Central

Fraser, Gareth J.; Bloomquist, Ryan F.; Streelman, J. Todd

2013-01-01

In many non-mammalian vertebrates, adult dentitions result from cyclical rounds of tooth regeneration wherein simple unicuspid teeth are replaced by more complex forms. Therefore and by contrast to mammalian models, the numerical majority of vertebrate teeth develop shape during the process of replacement. Here, we exploit the dental diversity of Lake Malawi cichlid fishes to ask how vertebrates generally replace their dentition and in turn how this process acts to influence resulting tooth morphologies. First, we used immunohistochemistry to chart organogenesis of continually replacing cichlid teeth and discovered an epithelial down-growth that initiates the replacement cycle via a labial proliferation bias. Next, we identified sets of co-expressed genes from common pathways active during de novo, lifelong tooth replacement and tooth morphogenesis. Of note, we found two distinct epithelial cell populations, expressing markers of dental competence and cell potency, which may be responsible for tooth regeneration. Related gene sets were simultaneously active in putative signaling centers associated with the differentiation of replacement teeth with complex shapes. Finally, we manipulated targeted pathways (BMP, FGF, Hh, Notch, Wnt/β-catenin) in vivo with small molecules and demonstrated dose-dependent effects on both tooth replacement and tooth shape. Our data suggest that the processes of tooth regeneration and tooth shape morphogenesis are integrated via a common set of molecular signals. This linkage has subsequently been lost or decoupled in mammalian dentitions where complex tooth shapes develop in first generation dentitions that lack the capacity for lifelong replacement. Our dissection of the molecular mechanics of vertebrate tooth replacement coupled to complex shape pinpoints aspects of odontogenesis that might be re-evolved in the lab to solve problems in regenerative dentistry. PMID:23422830

[Klippel-Feil syndrome with tracheoesophageal fistula, bifid thumb and cerebral angiolipoma.

PubMed

Urdaneta Carruyo, Eliéxer; Rojas Zerpa, Gustavo; Urdaneta Contreras, Adriana; Maldonado Alviarez, Malvy; Brito Rodríguez, Miguel

2016-12-01

The Klippel-Feil syndrome is a congenital malformation of the skull flap involving complex cervical vertebrae and organs, characterized by a classic triad: short neck, limitation of movement of the head due to cervical spine fusion and low hairline in occipital region. It results from an error in the axial skeleton segmentation of the embryo; its incidence is estimated at 1/40,000-42,000 births and predominates in females. The aim of this paper is to describe the clinical picture of a patient with Klippel-Feil syndrome and multiple malformations, including tracheoesophageal fistula, bifid thumb and intracranial lipomas/angiolipomas,that have not been previously described in the syndrome, so it is considered an exceptional finding. Sociedad Argentina de Pediatría.

Modern classification and outcome predictors of surgery in patients with brain arteriovenous malformations.

PubMed

Tayebi Meybodi, Ali; Lawton, Michael T

2018-02-23

Brain arteriovenous malformations (bAVM) are challenging lesions. Part of this challenge stems from the infinite diversity of these lesions regarding shape, location, anatomy, and physiology. This diversity has called on a variety of treatment modalities for these lesions, of which microsurgical resection prevails as the mainstay of treatment. As such, outcome prediction and managing strategy mainly rely on unraveling the nature of these complex tangles and ways each lesion responds to various therapeutic modalities. This strategy needs the ability to decipher each lesion through accurate and efficient categorization. Therefore, classification schemes are essential parts of treatment planning and outcome prediction. This article summarizes different surgical classification schemes and outcome predictors proposed for bAVMs.

Examination of products of conception terminated after prenatal investigation.

PubMed Central

Knowles, S

1986-01-01

A large number of district general hospitals have access to diagnostic ultrasonography and other methods of prenatal diagnosis, resulting in an increased supply of freshly terminated malformed fetuses to general histopathology departments, and there is now more open discussion of malformation and greater concern over fetal wastage. General pathologists are therefore under greater pressure to produce complete and detailed descriptions of a wide range of often complex anomalies. The dismissal of specimens as "multiple congenital anomalies" is becoming increasingly unacceptable to couples who wish to embark on further pregnancies and to their medical attendants. As in other fields an understanding of the methods and terminology in clinical use and a consistent diagnostic approach should help pathologists to extract sufficient information for accurate counselling. Images PMID:3537013

The insect nephrocyte is a podocyte-like cell with a filtration slit diaphragm

PubMed Central

Weavers, Helen; Prieto-Sánchez, Silvia; Grawe, Ferdinand; Garcia-López, Amparo; Artero, Ruben; Wilsch-Braeuninger, Michaela; Ruiz-Gómez, Mar; Skaer, Helen; Denholm, Barry

2009-01-01

The nephron is the basic structural and functional unit of the vertebrate kidney. It is composed of a glomerulus, the site of ultrafiltration, and a renal tubule, along which the filtrate is modified. Although widely regarded as a vertebrate adaptation1 ‘nephron-like’ features can be found in the excretory systems of many invertebrates, raising the possibility that components of the vertebrate excretory system were inherited from their invertebrate ancestors2. Here we show that the insect nephrocyte has remarkable anatomical, molecular and functional similarity with the glomerular podocyte, a cell in the vertebrate kidney that forms the main size-selective barrier as blood is ultrafiltered to make urine. In particular, both cell types possess a specialised filtration diaphragm, known as the slit diaphragm in podocytes or the nephrocyte diaphragm in nephrocytes. We find that fly orthologues of the major constituents of the slit diaphragm, including nephrin, neph1, CD2AP, ZO-1 and podocin are expressed in the nephrocyte and form a complex of interacting proteins that closely mirrors the vertebrate slit diaphragm complex. Furthermore, we find the nephrocyte diaphragm is completely lost in flies mutant for nephrin or neph1 orthologues, a phenotype resembling loss of the slit diaphragm in the absence of either nephrin (as in the human kidney disease NPHS1) or neph1. These changes drastically impair filtration function in the nephrocyte. The similarities we describe between invertebrate nephrocytes and vertebrate podocytes provide evidence suggesting the two cell types are evolutionarily related and establish the nephrocyte as a simple model in which to study podocyte biology and podocyte-associated diseases. PMID:18971929

The evolution of vertebral formulae in Hominoidea.

PubMed

Thompson, Nathan E; Almécija, Sergio

2017-09-01

Primate vertebral formulae have long been investigated because of their link to locomotor behavior and overall body plan. Knowledge of the ancestral vertebral formulae in the hominoid tree of life is necessary to interpret the pattern of evolution among apes, and to critically evaluate the morphological adaptations involved in the transition to hominin bipedalism. Though many evolutionary hypotheses have been proposed based on living and fossil species, the application of quantitative phylogenetic methods for thoroughly reconstructing ancestral vertebral formulae and formally testing patterns of vertebral evolution is lacking. To estimate the most probable scenarios of hominoid vertebral evolution, we utilized an iterative ancestral state reconstruction approach to determine likely ancestral vertebral counts in apes, humans, and other anthropoid out-groups. All available ape and hominin fossil taxa with an inferred regional vertebral count were included in the analysis. Sensitivity iterations were performed both by changing the phylogenetic position of fossil taxa with a contentious placement, and by changing the inferred number of vertebrae in taxa with uncertain morphology. Our ancestral state reconstruction results generally support a short-backed hypothesis of human evolution, with a Pan-Homo last common ancestor possessing a vertebral formulae of 7:13:4:6 (cervical:thoracic:lumbar:sacral). Our results indicate that an initial reduction in lumbar vertebral count and increase in sacral count is a synapomorphy of crown hominoids (supporting an intermediate-backed hypothesis for the origins of the great ape-human clade). Further reduction in lumbar count occurs independently in orangutans and African apes. Our results highlight the complexity and homoplastic nature of vertebral count evolution, and give little support to the long-backed hypothesis of human evolution. Copyright © 2017 Elsevier Ltd. All rights reserved.

Magnetic Resonance Imaging of Malformations of Midbrain-Hindbrain.

PubMed

Abdel Razek, Ahmed Abdel Khalek; Castillo, Mauricio

2016-01-01

We aim to review the magnetic resonance imaging appearance of malformations of midbrain and hindbrain. These can be classified as predominantly cerebellar malformations, combined cerebellar and brain stem malformations, and predominantly brain stem malformations. The diagnostic criteria for the majority of these morphological malformations are based on neuroimaging findings. The predominantly cerebellar malformations include predominantly vermian hypoplasia seen in Dandy-Walker malformation and rhombencephalosynapsis, global cerebellar hypoplasia reported in lissencephaly and microlissencephaly, and unilateral cerebellar hypoplasia seen in PHACES, vanishing cerebellum, and cerebellar cleft. Cerebellar dysplasias are seen in Chudley-McCullough syndrome, associated with LAMA1 mutations and GPR56 mutations; Lhermitte-Duclos disease; and focal cerebellar dysplasias. Cerebellar hyperplasias are seen in megalencephaly-related syndromes and hemimegalencephaly with ipsilateral cerebellomegaly. Cerebellar and brain stem malformations include tubulinopathies, Joubert syndrome, cobblestone malformations, pontocerebellar hypoplasias, and congenital disorders of glycosylation type Ia. Predominantly brain stem malformations include congenital innervation dysgenesis syndrome, pontine tegmental cap dysplasia, diencephalic-mesencephalic junction dysplasia, disconnection syndrome, and pontine clefts.

Comparative genomic analysis of the MHC: the evolution of class I duplication blocks, diversity and complexity from shark to man.

PubMed

Kulski, Jerzy K; Shiina, Takashi; Anzai, Tatsuya; Kohara, Sakae; Inoko, Hidetoshi

2002-12-01

The major histocompatibility complex (MHC) genomic region is composed of a group of linked genes involved functionally with the adaptive and innate immune systems. The class I and class II genes are intrinsic features of the MHC and have been found in all the jawed vertebrates studied so far. The MHC genomic regions of the human and the chicken (B locus) have been fully sequenced and mapped, and the mouse MHC sequence is almost finished. Information on the MHC genomic structures (size, complexity, genic and intergenic composition and organization, gene order and number) of other vertebrates is largely limited or nonexistent. Therefore, we are mapping, sequencing and analyzing the MHC genomic regions of different human haplotypes and at least eight nonhuman species. Here, we review our progress with these sequences and compare the human MHC structure with that of the nonhuman primates (chimpanzee and rhesus macaque), other mammals (pigs, mice and rats) and nonmammalian vertebrates such as birds (chicken and quail), bony fish (medaka, pufferfish and zebrafish) and cartilaginous fish (nurse shark). This comparison reveals a complex MHC structure for mammals and a relatively simpler design for nonmammalian animals with a hypothetical prototypic structure for the shark. In the mammalian MHC, there are two to five different class I duplication blocks embedded within a framework of conserved nonclass I and/or nonclass II genes. With a few exceptions, the class I framework genes are absent from the MHC of birds, bony fish and sharks. Comparative genomics of the MHC reveal a highly plastic region with major structural differences between the mammalian and nonmammalian vertebrates. Additional genomic data are needed on animals of the reptilia, crocodilia and marsupial classes to find the origins of the class I framework genes and examples of structures that may be intermediate between the simple and complex MHC organizations of birds and mammals, respectively.

Can simple rules control development of a pioneer vertebrate neuronal network generating behavior?

PubMed

Roberts, Alan; Conte, Deborah; Hull, Mike; Merrison-Hort, Robert; al Azad, Abul Kalam; Buhl, Edgar; Borisyuk, Roman; Soffe, Stephen R

2014-01-08

How do the pioneer networks in the axial core of the vertebrate nervous system first develop? Fundamental to understanding any full-scale neuronal network is knowledge of the constituent neurons, their properties, synaptic interconnections, and normal activity. Our novel strategy uses basic developmental rules to generate model networks that retain individual neuron and synapse resolution and are capable of reproducing correct, whole animal responses. We apply our developmental strategy to young Xenopus tadpoles, whose brainstem and spinal cord share a core vertebrate plan, but at a tractable complexity. Following detailed anatomical and physiological measurements to complete a descriptive library of each type of spinal neuron, we build models of their axon growth controlled by simple chemical gradients and physical barriers. By adding dendrites and allowing probabilistic formation of synaptic connections, we reconstruct network connectivity among up to 2000 neurons. When the resulting "network" is populated by model neurons and synapses, with properties based on physiology, it can respond to sensory stimulation by mimicking tadpole swimming behavior. This functioning model represents the most complete reconstruction of a vertebrate neuronal network that can reproduce the complex, rhythmic behavior of a whole animal. The findings validate our novel developmental strategy for generating realistic networks with individual neuron- and synapse-level resolution. We use it to demonstrate how early functional neuronal connectivity and behavior may in life result from simple developmental "rules," which lay out a scaffold for the vertebrate CNS without specific neuron-to-neuron recognition.

Microdisc gel electrophoresis in sodium dodecyl sulfate of organic material from rat otoconial complexes

NASA Technical Reports Server (NTRS)

Ross, M. D.; Pote, K. G.; Rarey, K. E.; Verma, L. M.

1981-01-01

The gravity receptors of all vertebrates utilize a 'test mass' consisting of a complex arrangement of mineral and organic substance that lies over the sensory receptor areas. In most vertebrates, the mineral is a polymorph of calcium carbonate in the form of minute, single crystals called otoconia. An investigation is conducted to determine the number of proteins in otoconial complexes and their molecular weights. The investigation makes use of a microdisk gel electrophoresis method reported by Gainer (1971). The most important finding of the reported research is that analysis of the proteins of the organic material of the otoconial complexes is possible when sensitive microanalytical methods are employed. Further modification of the basic technique employed and the inclusion of other sensitive staining methods should mean that, in the future, protein separation by molecular weight will be possible in sample pools containing only two otoconial masses.

Ontogenetic niche shifts in dinosaurs influenced size, diversity and extinction in terrestrial vertebrates.

PubMed

Codron, Daryl; Carbone, Chris; Müller, Dennis W H; Clauss, Marcus

2012-08-23

Given the physiological limits to egg size, large-bodied non-avian dinosaurs experienced some of the most extreme shifts in size during postnatal ontogeny found in terrestrial vertebrate systems. In contrast, mammals--the other dominant vertebrate group since the Mesozoic--have less complex ontogenies. Here, we develop a model that quantifies the impact of size-specific interspecies competition on abundances of differently sized dinosaurs and mammals, taking into account the extended niche breadth realized during ontogeny among large oviparous species. Our model predicts low diversity at intermediate size classes (between approx. 1 and 1000 kg), consistent with observed diversity distributions of dinosaurs, and of Mesozoic land vertebrates in general. It also provides a mechanism--based on an understanding of different ecological and evolutionary constraints across vertebrate groups--that explains how mammals and birds, but not dinosaurs, were able to persist beyond the Cretaceous-Tertiary (K-T) boundary, and how post-K-T mammals were able to diversify into larger size categories.

Ontogenetic niche shifts in dinosaurs influenced size, diversity and extinction in terrestrial vertebrates

PubMed Central

Codron, Daryl; Carbone, Chris; Müller, Dennis W. H.; Clauss, Marcus

2012-01-01

Given the physiological limits to egg size, large-bodied non-avian dinosaurs experienced some of the most extreme shifts in size during postnatal ontogeny found in terrestrial vertebrate systems. In contrast, mammals—the other dominant vertebrate group since the Mesozoic—have less complex ontogenies. Here, we develop a model that quantifies the impact of size-specific interspecies competition on abundances of differently sized dinosaurs and mammals, taking into account the extended niche breadth realized during ontogeny among large oviparous species. Our model predicts low diversity at intermediate size classes (between approx. 1 and 1000 kg), consistent with observed diversity distributions of dinosaurs, and of Mesozoic land vertebrates in general. It also provides a mechanism—based on an understanding of different ecological and evolutionary constraints across vertebrate groups—that explains how mammals and birds, but not dinosaurs, were able to persist beyond the Cretaceous–Tertiary (K–T) boundary, and how post-K–T mammals were able to diversify into larger size categories. PMID:22513279

A platform for rapid exploration of aging and diseases in a naturally short-lived vertebrate

PubMed Central

Harel, Itamar; Benayoun, Bérénice A.; Machado, Ben; Singh, Param Priya; Hu, Chi-Kuo; Pech, Matthew F.; Valenzano, Dario R.; Zhang, Elisa; Sharp, Sabrina C.; Artandi, Steven E.; Brunet, Anne

2015-01-01

Summary Aging is a complex process that affects multiple organs. Modeling aging and age-related diseases in the lab is challenging because classical vertebrate models have relatively long lifespans. Here we develop the first platform for rapid exploration of age-dependent traits and diseases in vertebrates, using the naturally short-lived African turquoise killifish. We provide an integrative genomic and genome-editing toolkit in this organism using our de novo-assembled genome and the CRISPR/Cas9 technology. We mutate many genes encompassing the hallmarks of aging, and for a subset, we produce stable lines within 2–3 months. As a proof-of-principle, we show that fish deficient for the protein subunit of telomerase exhibit the fastest onset of telomere-related pathologies among vertebrates. We further demonstrate the feasibility of creating specific genetic variants. This genome-to-phenotype platform represents a unique resource for studying vertebrate aging and disease in a high throughput manner and for investigating candidates arising from human genome-wide studies. PMID:25684364

Vector-virus interactions and transmission dynamics of West Nile virus.

PubMed

Ciota, Alexander T; Kramer, Laura D

2013-12-09

West Nile virus (WNV; Flavivirus; Flaviviridae) is the cause of the most widespread arthropod-borne viral disease in the world and the largest outbreak of neuroinvasive disease ever observed. Mosquito-borne outbreaks are influenced by intrinsic (e.g., vector and viral genetics, vector and host competence, vector life-history traits) and extrinsic (e.g., temperature, rainfall, human land use) factors that affect virus activity and mosquito biology in complex ways. The concept of vectorial capacity integrates these factors to address interactions of the virus with the arthropod host, leading to a clearer understanding of their complex interrelationships, how they affect transmission of vector-borne disease, and how they impact human health. Vertebrate factors including host competence, population dynamics, and immune status also affect transmission dynamics. The complexity of these interactions are further exacerbated by the fact that not only can divergent hosts differentially alter the virus, but the virus also can affect both vertebrate and invertebrate hosts in ways that significantly alter patterns of virus transmission. This chapter concentrates on selected components of the virus-vector-vertebrate interrelationship, focusing specifically on how interactions between vector, virus, and environment shape the patterns and intensity of WNV transmission.

Vector-Virus Interactions and Transmission Dynamics of West Nile Virus

PubMed Central

Ciota, Alexander T.; Kramer, Laura D.

2013-01-01

West Nile virus (WNV; Flavivirus; Flaviviridae) is the cause of the most widespread arthropod-borne viral disease in the world and the largest outbreak of neuroinvasive disease ever observed. Mosquito-borne outbreaks are influenced by intrinsic (e.g., vector and viral genetics, vector and host competence, vector life-history traits) and extrinsic (e.g., temperature, rainfall, human land use) factors that affect virus activity and mosquito biology in complex ways. The concept of vectorial capacity integrates these factors to address interactions of the virus with the arthropod host, leading to a clearer understanding of their complex interrelationships, how they affect transmission of vector-borne disease, and how they impact human health. Vertebrate factors including host competence, population dynamics, and immune status also affect transmission dynamics. The complexity of these interactions are further exacerbated by the fact that not only can divergent hosts differentially alter the virus, but the virus also can affect both vertebrate and invertebrate hosts in ways that significantly alter patterns of virus transmission. This chapter concentrates on selected components of the virus-vector-vertebrate interrelationship, focusing specifically on how interactions between vector, virus, and environment shape the patterns and intensity of WNV transmission. PMID:24351794

Sparse intervertebral fence composition for 3D cervical vertebra segmentation

NASA Astrophysics Data System (ADS)

Liu, Xinxin; Yang, Jian; Song, Shuang; Cong, Weijian; Jiao, Peifeng; Song, Hong; Ai, Danni; Jiang, Yurong; Wang, Yongtian

2018-06-01

Statistical shape models are capable of extracting shape prior information, and are usually utilized to assist the task of segmentation of medical images. However, such models require large training datasets in the case of multi-object structures, and it also is difficult to achieve satisfactory results for complex shapes. This study proposed a novel statistical model for cervical vertebra segmentation, called sparse intervertebral fence composition (SiFC), which can reconstruct the boundary between adjacent vertebrae by modeling intervertebral fences. The complex shape of the cervical spine is replaced by a simple intervertebral fence, which considerably reduces the difficulty of cervical segmentation. The final segmentation results are obtained by using a 3D active contour deformation model without shape constraint, which substantially enhances the recognition capability of the proposed method for objects with complex shapes. The proposed segmentation framework is tested on a dataset with CT images from 20 patients. A quantitative comparison against corresponding reference vertebral segmentation yields an overall mean absolute surface distance of 0.70 mm and a dice similarity index of 95.47% for cervical vertebral segmentation. The experimental results show that the SiFC method achieves competitive cervical vertebral segmentation performances, and completely eliminates inter-process overlap.

Back to basics--how the evolution of the extracellular matrix underpinned vertebrate evolution.

PubMed

Huxley-Jones, Julie; Pinney, John W; Archer, John; Robertson, David L; Boot-Handford, Raymond P

2009-04-01

The extracellular matrix (ECM) is a complex substrate that is involved in and influences a spectrum of behaviours such as growth and differentiation and is the basis for the structure of tissues. Although a characteristic of all metazoans, the ECM has elaborated into a variety of tissues unique to vertebrates, such as bone, tendon and cartilage. Here we review recent advances in our understanding of the molecular evolution of the ECM. Furthermore, we demonstrate that ECM genes represent a pivotal family of proteins the evolution of which appears to have played an important role in the evolution of vertebrates.

Comparative anatomy of the autonomic nervous system.

PubMed

Nilsson, Stefan

2011-11-16

This short review aims to point out the general anatomical features of the autonomic nervous systems of non-mammalian vertebrates. In addition it attempts to outline the similarities and also the increased complexity of the autonomic nervous patterns from fish to tetrapods. With the possible exception of the cyclostomes, perhaps the most striking feature of the vertebrate autonomic nervous system is the similarity between the vertebrate classes. An evolution of the complexity of the system can be seen, with the segmental ganglia of elasmobranchs incompletely connected longitudinally, while well developed paired sympathetic chains are present in teleosts and the tetrapods. In some groups the sympathetic chains may be reduced (dipnoans and caecilians), and have yet to be properly described in snakes. Cranial autonomic pathways are present in the oculomotor (III) and vagus (X) nerves of gnathostome fish and the tetrapods, and with the evolution of salivary and lachrymal glands in the tetrapods, also in the facial (VII) and glossopharyngeal (IX) nerves. Copyright © 2010 Elsevier B.V. All rights reserved.

Congenital heart defects in newborns with apparently isolated single gastrointestinal malformation: A retrospective study.

PubMed

Schierz, Ingrid Anne Mandy; Pinello, Giuseppa; Giuffrè, Mario; La Placa, Simona; Piro, Ettore; Corsello, Giovanni

2016-12-01

Congenital gastrointestinal system malformations/abdominal wall defects (GISM) may appear as isolated defects (single or complex), or in association with multiple malformations. The high incidence of association of GISM and congenital heart defects (CHD) in patients with syndromes and malformative sequences is known, but less expected is the association of apparently isolated single GISM and CHD. The aim of this study was to investigate the frequency of CHD in newborns with isolated GISM, and the possibility to modify the diagnostic-therapeutic approach just before the onset of cardiac symptoms or complications. Anamnestic, clinical, and imaging data of newborns requiring abdominal surgery for GISM, between 2009 and 2014, were compared with a control group of healthy newborns. Distribution of GISM and cardiovascular abnormalities were analyzed, and risk factors for adverse outcomes were identified. Seventy-one newborns with isolated GISM were included in this study. More frequent GISM were intestinal rotation and fixation disorders. CHD were observed in 15.5% of patients, augmenting their risk for morbidity. Risk factors for morbidity related to sepsis were identified in central venous catheter, intestinal stoma, and H2-inhibitor-drugs. Moreover, 28.2% of newborns presented only functional cardiac disorders but an unexpectedly higher mortality. The high incidence of congenital heart disease in infants with apparently isolated GISM confirms the need to perform an echocardiographic study before surgery to improve perioperative management and prevent complications such as sepsis and endocarditis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Fused lobed anther and hooked stigma affect pollination, fertilization and fruit set in mango: a scanning electron microscopy study.

PubMed

Rani, Varsha; Ansari, Mohammad Wahid; Shukla, Alok; Tuteja, Narendra; Bains, Gurdeep

2013-03-01

Mango malformation is the most threaten disease that limits mango production, worldwide. For a long time, due to its complex nature, the cause and causal agents were strongly disputed. Diverse Fusaria, including Fusarium mangiferae, are known to be associated with the disease. There are indications that augmented level of endogenous ethylene in response to various abiotic and biotic stresses alters the morphology of reproductive organs. Here, scanning electron microscopy (SEM) of healthy and malformed reproductive organs of mango cv. Baramasi was performed to compare the functional morphology. The SEM study revealed that anthers of hermaphrodite healthy flowers were bilobed with large number of turgid pollen grains whereas malformed flowers showed fused lobed anthers with scanty deformed pollen grains. Furthermore, the stigma of healthy flowers exhibited a broad landing pad as compared to malformed stigma which showed hooked and pointed tip. All these impaired morphology of male and female reproductive organs lead to failure of sexual reproduction. This is the first evidence to show fused lobed anther with impaired pollen grains and hooked stigma with poor stigmatic receptivity are mainly responsible for restricting the pollen germination and pollen tube growth. Here we suggest that abnormal development of anthers and pistils is due to endogenously produced stress ethylene. Further, added load of cyanide, a byproduct of ethylene biosynthesis, may also contribute to the development of necrosis which lead to desiccation of anther and pistil during hypersensitive response of plants.

An open-label study to evaluate sildenafil for the treatment of lymphatic malformations.

PubMed

Danial, Christina; Tichy, Andrea L; Tariq, Umar; Swetman, Glenda L; Khuu, Phuong; Leung, Thomas H; Benjamin, Latanya; Teng, Joyce; Vasanawala, Shreyas S; Lane, Alfred T

2014-06-01

Lymphatic malformations can be challenging to treat. Mainstay interventions including surgery and sclerotherapy are invasive and can result in local recurrence and complications. We sought to assess the effect of 20 weeks of oral sildenafil on reducing lymphatic malformation volume and symptoms in children. Seven children (4 boys, 3 girls; ages 13-85 months) with lymphatic malformations were given oral sildenafil for 20 weeks in this open-label study. The volume of the lymphatic malformation was calculated blindly using magnetic resonance imaging performed before and after 20 weeks of sildenafil. Lymphatic malformations were assessed clinically on weeks 4, 12, 20, and 32. Both the physician and parents evaluated the lymphatic malformation in comparison with baseline. Four subjects had a lymphatic malformation volume decrease (1.0%-31.7%). In 2 subjects, despite a lymphatic malformation volume increase (1.1%-3.7%), clinical improvement was noted while on sildenafil. One subject had a 29.6% increase in lymphatic malformation volume and no therapeutic response. Lymphatic malformations of all 6 subjects who experienced a therapeutic response on sildenafil softened and became easily compressible. Adverse events were minimal. A randomized controlled trial will be necessary to verify the effects of sildenafil on lymphatic malformations. Sildenafil can reduce lymphatic malformation volume and symptoms in some children. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Unusual Association: Cerebral Arteriovenous Malformation and Chiari Type I Malformation.

PubMed

Ogul, Hayri; Kantarci, Mecit

2017-06-01

Cerebral arteriovenous malformation (AVM) is a common type of cerebral vascular malformation. The imaging findings are enlarged vessels, thrombosed sinuses, and hemorrhage or gliosis on adjacent brain parenchyma. Magnetic resonance (MR) imaging can be used safely for diagnosis. Chiari type I malformation is characterized by a caudal descent of the cerebellar tonsil. Coincidence of cerebral AVM and Chiari type I malformation is very rare. In this paper, the authors report MR imaging findings of a patient with coincidence of cerebral AVM and Chiari type I malformation.

Unjoined primary and secondary neural tubes: junctional neural tube defect, a new form of spinal dysraphism caused by disturbance of junctional neurulation.

PubMed

Eibach, Sebastian; Moes, Greg; Hou, Yong Jin; Zovickian, John; Pang, Dachling

2017-10-01

Primary and secondary neurulation are the two known processes that form the central neuraxis of vertebrates. Human phenotypes of neural tube defects (NTDs) mostly fall into two corresponding categories consistent with the two types of developmental sequence: primary NTD features an open skin defect, an exposed, unclosed neural plate (hence an open neural tube defect, or ONTD), and an unformed or poorly formed secondary neural tube, and secondary NTD with no skin abnormality (hence a closed NTD) and a malformed conus caudal to a well-developed primary neural tube. We encountered three cases of a previously unrecorded form of spinal dysraphism in which the primary and secondary neural tubes are individually formed but are physically separated far apart and functionally disconnected from each other. One patient was operated on, in whom both the lumbosacral spinal cord from primary neurulation and the conus from secondary neurulation are each anatomically complete and endowed with functioning segmental motor roots tested by intraoperative triggered electromyography and direct spinal cord stimulation. The remarkable feature is that the two neural tubes are unjoined except by a functionally inert, probably non-neural band. The developmental error of this peculiar malformation probably occurs during the critical transition between the end of primary and the beginning of secondary neurulation, in a stage aptly called junctional neurulation. We describe the current knowledge concerning junctional neurulation and speculate on the embryogenesis of this new class of spinal dysraphism, which we call junctional neural tube defect.

Analysis of renal anomalies in VACTERL association.

PubMed

Cunningham, Bridget K; Khromykh, Alina; Martinez, Ariel F; Carney, Tyler; Hadley, Donald W; Solomon, Benjamin D

2014-10-01

VACTERL association refers to a combination of congenital anomalies that can include: vertebral anomalies, anal atresia, cardiac malformations, tracheo-esophageal fistula with esophageal atresia, renal anomalies (typically structural renal anomalies), and limb anomalies. We conducted a description of a case series to characterize renal findings in a cohort of patients with VACTERL association. Out of the overall cohort, 48 patients (with at least three component features of VACTERL and who had abdominal ultrasound performed) met criteria for analysis. Four other patients were additionally analyzed separately, with the hypothesis that subtle renal system anomalies may occur in patients who would not otherwise meet criteria for VACTERL association. Thirty-three (69%) of the 48 patients had a clinical manifestation affecting the renal system. The most common renal manifestation (RM) was vesicoureteral reflux (VUR) in addition to a structural defect (present in 27%), followed by unilateral renal agenesis (24%), and then dysplastic/multicystic kidneys or duplicated collected system (18% for each). Twenty-two (88%) of the 25 patients with a structural RM had an associated anorectal malformation. Individuals with either isolated lower anatomic anomalies, or both upper and lower anatomic anomalies were not statistically more likely to have a structural renal defect than those with isolated upper anatomic anomalies (p = 0.22, p = 0.284, respectively). Given the high prevalence of isolated VUR in our cohort, we recommend a screening VCUG or other imaging modality be obtained to evaluate for VUR if initial renal ultrasound shows evidence of obstruction or renal scarring, as well as ongoing evaluation of renal health. © 2014 Wiley Periodicals, Inc.

The effect of adriamycin exposure on the notochord of mouse embryos.

PubMed

Hajduk, Piotr; May, Alison; Puri, Prem; Murphy, Paula

2012-04-01

The notochord has important structural and signaling properties during vertebrate development with key roles in patterning surrounding tissues, including the foregut. The adriamycin mouse model is an established model of foregut anomalies where exposure of embryos in utero to the drug adriamycin leads to malformations including oesophageal atresia and tracheoesophageal fistula. In addition to foregut abnormalities, treatment also causes branching, displacement, and hypertrophy of the notochord. Here, we explore the hypothesis that the notochord may be a primary target of disruption leading to abnormal patterning of the foregut by examining notochord position and structure in early embryos following adriamycin exposure. Treated (n = 46) and control (n = 30) embryos were examined during the crucial period when the notochord normally delaminates away from the foregut endoderm (6-28 somite pairs). Transverse sections were derived from the anterior foregut and analyzed by confocal microscopy following immunodetection of extracellular matrix markers E-cadherin and Laminin. In adriamycin-treated embryos across all stages, the notochord was abnormally displaced ventrally with prolonged attachment to the foregut endoderm. While E-cadherin was normally detected in the foregut endoderm with no expression in the notochord of control embryos, treated embryos up to 24 somites showed ectopic notochordal expression indicating a change in characteristics of the tissue; specifically an increase in intracellular adhesiveness, which may be instrumental in structural changes, affecting mechanical and signaling properties. This is consistent with disruption of the notochord leading to altered signaling to the foregut causing abnormal patterning and congenital foregut malformations. © 2012 Wiley Periodicals, Inc.

Dumbbell-Shaped Epidural Capillary Hemangioma Presenting as a Lung Mass: Case Report and Review of the Literature.

PubMed

García-Pallero, María A; Torres, Cristina V; García-Navarrete, Eduardo; Gordillo, Carlos; Delgado, Juan; Penanes, Juan R; García-Campos, María T; Sola, R G

2015-07-15

A case report and literature review. We present the fourth case of a spinal epidural capillary hemangioma with a dumbbell-shaped appearance in the magnetic resonance image reported in the literature and the second presented as a lung mass. Hemangiomas are congenital vascular malformations that pathologists frequently consider to be hamartomatous malformations. Hemangiomas of the spine are usually lesions of the vertebral bodies, but they can sit in other locations such as the intramedullary or epidural space. Purely epidural hemangiomas are rare and most of them are of cavernous type. We present a 67-year-old female with a thoracic dumbbell-shaped capillary hemangioma with both foraminal and intrathoracic extensions, whose presentation was pleural effusion associated with mediastinal mass suggestive of pulmonary neoplasia. Surgical treatment consisted of total removal en bloc of the lesion. Microscopic evaluation showed a fibrofatty tissue with a proliferation of vascular structures that were generally of a small size, with areas of myxoid appearance. To date, there have been 8 epidural capillary hemangiomas of the thoracic and lumbar spine reported in the literature, and only 3 of them were dumbbell-shaped with extraforaminal extension. It is important to consider the diagnosis of hemangiomas in the differential diagnosis of epidural lesions with dumbbell-shaped appearance in the magnetic resonance image, especially at the thoracic level. It is a benign and potentially curable disease and the most appropriate surgical treatment is en bloc resection of the entire lesion. They are usually presented as a progressive myelopathy, so early treatment may prevent permanent neurological deficits. 5.

Time-of-flight magnetic resonance angiography imaging of a residual arteriovenous malformation nidus after Onyx embolization for stereotactic radiosurgery planning. Technical note.

PubMed

Loy, David N; Rich, Keith M; Simpson, Joseph; Dorward, Ian; Santanam, Lakshmi; Derdeyn, Colin P

2009-05-01

This report demonstrates that time-of-flight (TOF) MR angiography is a useful adjunct for planning stereotactic radiosurgery (SRS) of large arteriovenous malformations (AVMs) after staged embolization with Onyx. Onyx (ethylene vinyl copolymer), a recently approved liquid embolic agent, has been increasingly used to exclude portions of large AVMs from the parent circulation prior to SRS. Limiting SRS to regions of persistent arteriovenous shunting and excluding regions eliminated by embolization may reduce unnecessary radiation doses to eloquent brain structures. However, SRS dosimetry planning presents unique challenges after Onyx embolization because it creates extensive artifacts on CT scans, and it cannot be delineated from untreated nidus on standard MR sequences. During the radiosurgery procedure, MR images were obtained using a GE Signa 1.5-T unit. Standard axial T2 fast spin echo high-resolution images (TR 3000 msec, TE 108 msec, slice thickness 2.5 mm) were generated for optimal visualization of brain tissue and AVM flow voids. The 3D TOF MR angiography images of the circle of Willis and vertebral arteries were subsequently obtained to visualize AVM regions embolized with Onyx (TR 37 msec, TE 6.9 msec, flip angle 20 degrees). Adjunct TOF MR angiography images demonstrated excellent contrast between nidus embolized with Onyx and regions of persistent arteriovenous shunting within a large AVM prior to SRS. Additional information derived from these sequences resulted in substantial adjustments to the treatment plan and an overall reduction in the treated tissue volume.

Deprenyl Enhances the Teratogenicity of Hydroxyurea in Organogenesis Stage Mouse Embryos

PubMed Central

Schlisser, Ava E.; Hales, Barbara F.

2013-01-01

Hydroxyurea, an antineoplastic drug, is a model teratogen. The administration of hydroxyurea to CD1 mice on gestation day 9 induces oxidative stress, increasing the formation of 4-hydroxy-2-nonenal adducts to redox-sensitive proteins such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the caudal region of the embryo. GAPDH catalytic activity is reduced, and its translocation into the nucleus is increased. Because the nuclear translocation of GAPDH is associated with oxidative stress–induced cell death, we hypothesized that this translocation plays a role in mediating the teratogenicity of hydroxyurea. Deprenyl (also known as selegiline), a drug used as a neuroprotectant in Parkinson’s disease, inhibits the nuclear translocation of GAPDH. Hence, timed pregnant CD1 mice were treated with deprenyl (10mg/kg) on gestation day 9 followed by the administration of hydroxyurea (400 or 600mg/kg). Deprenyl treatment significantly decreased the hydroxyurea-induced nuclear translocation of GAPDH in the caudal lumbosacral somites. Deprenyl enhanced hydroxyurea-mediated caudal malformations, inducing specifically limb reduction, digit anomalies, tail defects, and lumbosacral vertebral abnormalities. Deprenyl did not augment the hydroxyurea-induced inhibition of glycolysis or alter the ratio of oxidized to reduced glutathione. However, it did dramatically increase cleaved caspase-3 in embryos. These data suggest that nuclear GAPDH plays an important, region-specific, role in teratogen-exposed embryos. Deprenyl exacerbated the developmental outcome of hydroxyurea exposure by a mechanism that is independent of oxidative stress. Although the administration of deprenyl alone did not affect pregnancy outcome, this drug may have adverse consequences when combined with exposures that increase the risk of malformations. PMID:23696560

Spectrum of prenatally detected central nervous system malformations: Neural tube defects continue to be the leading foetal malformation.

PubMed

Siddesh, Anjurani; Gupta, Geetika; Sharan, Ram; Agarwal, Meenal; Phadke, Shubha R

2017-04-01

Prenatal diagnosis of malformations is an important method of prevention and control of congenital anomalies with poor prognosis. Central nervous system (CNS) malformations amongst these are the most common. The information about the prevalence and spectrum of prenatally detected malformations is crucial for genetic counselling and policymaking for population-based preventive programmes. The objective of this study was to study the spectrum of prenatally detected CNS malformations and their association with chromosomal abnormalities and autopsy findings. This retrospective study was conducted in a tertiary care hospital in north India from January 2007 to December 2013. The details of cases with prenatally detected CNS malformations were collected and were related with the foetal chromosomal analysis and autopsy findings. Amongst 6044 prenatal ultrasonographic examinations performed; 768 (12.7%) had structural malformations and 243 (31.6%) had CNS malformations. Neural tube defects (NTDs) accounted for 52.3 per cent of CNS malformations and 16.5 per cent of all malformations. The other major groups of prenatally detected CNS malformations were ventriculomegaly and midline anomalies. Chromosomal abnormalities were detected in 8.2 per cent of the 73 cases studied. Foetal autopsy findings were available for 48 foetuses. Foetal autopsy identified additional findings in eight foetuses and the aetiological diagnosis changed in two of them (4.2%). Amongst prenatally detected malformations, CNS malformations were common. NTD, which largely is a preventable anomaly, continued to be the most common group. Moreover, 60 per cent of malformations were diagnosed after 20 weeks, posing legal issues. Chromosomal analysis and foetal autopsy are essential for genetic counselling based on aetiological diagnosis.

Disseminated Mycobacterium chimaera Presenting as Vertebral Osteomyelitis.

PubMed

Moutsoglou, Daphne M; Merritt, Frank; Cumbler, Ethan

2017-01-01

Mycobacterium chimaera , a member of the Mycobacterium avium complex, is a slow-growing, nontuberculous mycobacterium associated with outbreaks in cardiac-surgery patients supported on heart-lung machines. We report a case of an elderly woman on chronic prednisone who presented with a six-month history of worsening chronic back pain, recurrent low-grade fevers, and weight loss. Imaging identified multilevel vertebral osteomyelitis and lumbar soft-tissue abscess. Abscess culture identified M. chimaera .

The nature of cumulative impacts on biotic diversity of wetland vertebrates

NASA Astrophysics Data System (ADS)

Harris, Larry D.

1988-09-01

There is no longer any doubt that cumulative impacts have important effects on wetland vertebrates. Interactions of species diversity and community structure produce a complex pattern in which environmental impacts can play a highly significant role. Various examples show how wetlands maintain the biotic diversity within and among vertebrate populations, and some of the ways that environmental perturbations can interact to reduce this diversity. The trophic and habitat pyramids are useful organizing concepts. Habitat fragmentation can have severe effects at all levels, reducing the usable range of the larger habitat generalists while threatening the genetic integrity of small, isolated populations. The complexity of trophic interactions, and the propensity, or necessity, of vertebrates to switch from one food source to another—something we know little about—makes using food chain support as a variable for predicting environmental impacts very questionable. Historical instances illustrate the effects of the accumulation of impacts on vertebrates. At present it is nearly impossible to predict the result of three or more different kinds of perturbations, although long-range effects can be observed. One case in point is waterfowl; while their ingestion of lead shot, harvesting by hunters during migration, and loss of habitat have caused waterfowl populations to decline, the proportional responsibility of these factors has not been determined. Further examples show multiplicative effects of similar actions, effects with long time lags, diffuse processes in the landscape that may have concentrated effects on a component subsystem, and a variety of other interactions of increasing complexity. Not only is more information needed at all levels; impacts must be assessed on a landscape or regional scale to produce informed management decisions. I conclude that a system of replicate wetland reserves that are allowed to interact naturally with the surrounding landscape will be more effective in preserving biotic diversity than isolated sanctuaries.

Comparative Genomic Analysis of slc39a12/ZIP12: Insight into a Zinc Transporter Required for Vertebrate Nervous System Development

PubMed Central

Chowanadisai, Winyoo

2014-01-01

The zinc transporter ZIP12, which is encoded by the gene slc39a12, has previously been shown to be important for neuronal differentiation in mouse Neuro-2a neuroblastoma cells and primary mouse neurons and necessary for neurulation during Xenopus tropicalis embryogenesis. However, relatively little is known about the biochemical properties, cellular regulation, or the physiological role of this gene. The hypothesis that ZIP12 is a zinc transporter important for nervous system function and development guided a comparative genetics approach to uncover the presence of ZIP12 in various genomes and identify conserved sequences and expression patterns associated with ZIP12. Ortholog detection of slc39a12 was conducted with reciprocal BLAST hits with the amino acid sequence of human ZIP12 in comparison to the human paralog ZIP4 and conserved local synteny between genomes. ZIP12 is present in the genomes of almost all vertebrates examined, from humans and other mammals to most teleost fish. However, ZIP12 appears to be absent from the zebrafish genome. The discrimination of ZIP12 compared to ZIP4 was unsuccessful or inconclusive in other invertebrate chordates and deuterostomes. Splice variation, due to the inclusion or exclusion of a conserved exon, is present in humans, rats, and cows and likely has biological significance. ZIP12 also possesses many putative di-leucine and tyrosine motifs often associated with intracellular trafficking, which may control cellular zinc uptake activity through the localization of ZIP12 within the cell. These findings highlight multiple aspects of ZIP12 at the biochemical, cellular, and physiological levels with likely biological significance. ZIP12 appears to have conserved function as a zinc uptake transporter in vertebrate nervous system development. Consequently, the role of ZIP12 may be an important link to reported congenital malformations in numerous animal models and humans that are caused by zinc deficiency. PMID:25375179

Functional characterization of the vertebrate primary ureter: Structure and ion transport mechanisms of the pronephric duct in axolotl larvae (Amphibia)

PubMed Central

2010-01-01

Background Three kidney systems appear during vertebrate development: the pronephroi, mesonephroi and metanephroi. The pronephric duct is the first or primary ureter of these kidney systems. Its role as a key player in the induction of nephrogenic mesenchyme is well established. Here we investigate whether the duct is involved in urine modification using larvae of the freshwater amphibian Ambystoma mexicanum (axolotl) as model. Results We investigated structural as well as physiological properties of the pronephric duct. The key elements of our methodology were: using histology, light and transmission electron microscopy as well as confocal laser scanning microscopy on fixed tissue and applying the microperfusion technique on isolated pronephric ducts in combination with single cell microelectrode impalements. Our data show that the fully differentiated pronephric duct is composed of a single layered epithelium consisting of one cell type comparable to the principal cell of the renal collecting duct system. The cells are characterized by a prominent basolateral labyrinth and a relatively smooth apical surface with one central cilium. Cellular impalements demonstrate the presence of apical Na+ and K+ conductances, as well as a large K+ conductance in the basolateral cell membrane. Immunolabeling experiments indicate heavy expression of Na+/K+-ATPase in the basolateral labyrinth. Conclusions We propose that the pronephric duct is important for the subsequent modification of urine produced by the pronephros. Our results indicate that it reabsorbs sodium and secretes potassium via channels present in the apical cell membrane with the driving force for ion movement provided by the Na+/K+ pump. This is to our knowledge the first characterization of the pronephric duct, the precursor of the collecting duct system, which provides a model of cell structure and basic mechanisms for ion transport. Such information may be important in understanding the evolution of vertebrate kidney systems and human diseases associated with congenital malformations. PMID:20507566

In vivo genome-wide analysis of multiple tissues identifies gene regulatory networks, novel functions and downstream regulatory genes for Bapx1 and its co-regulation with Sox9 in the mammalian vertebral column.

PubMed

Chatterjee, Sumantra; Sivakamasundari, V; Yap, Sook Peng; Kraus, Petra; Kumar, Vibhor; Xing, Xing; Lim, Siew Lan; Sng, Joel; Prabhakar, Shyam; Lufkin, Thomas

2014-12-05

Vertebrate organogenesis is a highly complex process involving sequential cascades of transcription factor activation or repression. Interestingly a single developmental control gene can occasionally be essential for the morphogenesis and differentiation of tissues and organs arising from vastly disparate embryological lineages. Here we elucidated the role of the mammalian homeobox gene Bapx1 during the embryogenesis of five distinct organs at E12.5 - vertebral column, spleen, gut, forelimb and hindlimb - using expression profiling of sorted wildtype and mutant cells combined with genome wide binding site analysis. Furthermore we analyzed the development of the vertebral column at the molecular level by combining transcriptional profiling and genome wide binding data for Bapx1 with similarly generated data sets for Sox9 to assemble a detailed gene regulatory network revealing genes previously not reported to be controlled by either of these two transcription factors. The gene regulatory network appears to control cell fate decisions and morphogenesis in the vertebral column along with the prevention of premature chondrocyte differentiation thus providing a detailed molecular view of vertebral column development.

Reconstruction of the vertebrate ancestral genome reveals dynamic genome reorganization in early vertebrates.

PubMed

Nakatani, Yoichiro; Takeda, Hiroyuki; Kohara, Yuji; Morishita, Shinichi

2007-09-01

Although several vertebrate genomes have been sequenced, little is known about the genome evolution of early vertebrates and how large-scale genomic changes such as the two rounds of whole-genome duplications (2R WGD) affected evolutionary complexity and novelty in vertebrates. Reconstructing the ancestral vertebrate genome is highly nontrivial because of the difficulty in identifying traces originating from the 2R WGD. To resolve this problem, we developed a novel method capable of pinning down remains of the 2R WGD in the human and medaka fish genomes using invertebrate tunicate and sea urchin genes to define ohnologs, i.e., paralogs produced by the 2R WGD. We validated the reconstruction using the chicken genome, which was not considered in the reconstruction step, and observed that many ancestral proto-chromosomes were retained in the chicken genome and had one-to-one correspondence to chicken microchromosomes, thereby confirming the reconstructed ancestral genomes. Our reconstruction revealed a contrast between the slow karyotype evolution after the second WGD and the rapid, lineage-specific genome reorganizations that occurred in the ancestral lineages of major taxonomic groups such as teleost fishes, amphibians, reptiles, and marsupials.

Cerebellar Development and Disease

PubMed Central

Gleeson, Joseph G.

2008-01-01

Recent Advances The molecular control of cell type specification within the developing cerebellum as well as the genetic causes of the most common human developmental cerebellar disorders have long remained mysterious. Recent genetic lineage and loss-of-function data from mice have revealed unique and non-overlapping anatomical origins for GABAergic neurons from ventricular zone precursors and glutamatergic cell from rhombic lip precursors, mirroring distinct origins for these neurotransmitter-specific cell types in the cerebral cortex. Mouse studies elucidating the role of Ptf1a as a cerebellar ventricular zone GABerigic fate switch were actually preceded by the recognition that PTF1A mutations in humans cause cerebellar agenesis, a birth defect of the human cerebellum. Indeed, several genes for congenital human cerebellar malformations have recently been identified, including genes causing Joubert syndrome, Dandy-Walker malformation and Ponto-cerebellar hypoplasia. These studies have pointed to surprisingly complex roles for transcriptional regulation, mitochondrial function and neuronal cilia in patterning, homeostasis and cell proliferation during cerebellar development. Together mouse and human studies are synergistically advancing our understanding of the developmental mechanisms that generate the uniquely complex mature cerebellum. PMID:18513948

Male pregnancy and the evolution of body segmentation in seahorses and pipefishes.

PubMed

Hoffman, Eric A; Mobley, Kenyon B; Jones, Adam G

2006-02-01

The evolution of complex traits, which are specified by the interplay of multiple genetic loci and environmental effects, is a topic of central importance in evolutionary biology. Here, we show that body and tail vertebral numbers in fishes of the pipefish and seahorse family (Syngnathidae) can serve as a model for studies of quantitative trait evolution. A quantitative genetic analysis of body and tail vertebrae from field-collected families of the Gulf pipefish, Syngnathus scovelli, shows that both traits exhibit significantly positive additive genetic variance, with heritabilities of 0.75 +/- 0.13 (mean +/- standard error) and 0.46 +/- 0.18, respectively. We do not find any evidence for either phenotypic or genetic correlations between the two traits. Pipefish are characterized by male pregnancy, and phylogenetic consideration of body proportions suggests that the position of eggs on the pregnant male's body may have contributed to the evolution of vertebral counts. In terms of numbers of vertebrae, tail-brooding males have longer tails for a given trunk size than do trunk-brooding males. Overall, these results suggest that vertebral counts in pipefish are heritable traits, capable of a response to selection, and they may have experienced an interesting history of selection due to the phenomenon of male pregnancy. Given that these traits vary among populations within species as well as among species, they appear to provide an excellent model for further research on complex trait evolution. Body segmentation may thus afford excellent opportunities for comparative study of homologous complex traits among disparate vertebrate taxa.

Neurocutaneous melanosis and the Dandy-Walker complex: an uncommon but not so insignificant association.

PubMed

Marnet, Dominique; Vinchon, Matthieu; Mostofi, Keyvan; Catteau, Benoit; Kerdraon, Olivier; Dhellemmes, Patrick

2009-12-01

Neurocutaneous melanosis represents a rare congenital but nonheritable phakomatosis defined as the association of giant or multiple congenital nonmalignant melanocytic nevi with leptomeningeal melanosis or melanoma of the central nervous system. We describe the case of an adolescent with a giant congenital bathing trunk melanocytic nevus who developed progressive intracranial hypertension due to leptomeningeal melanosis confirmed by surgical biopsy. Brain and spine magnetic resonance images showed posterior fossa malformation compatible with the Dandy-Walker complex, hydrocephalus, and extensive enhancement of posterior fossa then spine. Shunt placement, corticotherapy, and chemotherapy were attempted leading to transient relief but the boy died 12 months after the onset of primary neurological symptoms. We discuss diagnosis, pathogenesis, management, and prognosis in the light of data from the recent literature. Neurocutaneous melanosis is considered to follow from neurulation disorders which could account for associated developmental malformations as the so-called Dandy-Walker complex. Cutaneous lesions are usually recognized at birth whereas neurological manifestations develop later. Numerous neurological symptoms have been reported according to extent of leptomeningeal and parenchymal infiltration. Whether magnetic resonance imaging of the neuroaxis represents the choice radiological exam, definite diagnosis relies upon the histological data obtained by mean of biopsy. Once symptomatic, surgical and medical measures remain palliative since death occurs within 3 years.

Tissue Specific Roles for the Ribosome Biogenesis Factor Wdr43 in Zebrafish Development

PubMed Central

Zhao, Chengtian; Andreeva, Viktoria; Gibert, Yann; LaBonty, Melissa; Lattanzi, Victoria; Prabhudesai, Shubhangi; Zhou, Yi; Zon, Leonard; McCann, Kathleen L.; Baserga, Susan; Yelick, Pamela C.

2014-01-01

During vertebrate craniofacial development, neural crest cells (NCCs) contribute to most of the craniofacial pharyngeal skeleton. Defects in NCC specification, migration and differentiation resulting in malformations in the craniofacial complex are associated with human craniofacial disorders including Treacher-Collins Syndrome, caused by mutations in TCOF1. It has been hypothesized that perturbed ribosome biogenesis and resulting p53 mediated neuroepithelial apoptosis results in NCC hypoplasia in mouse Tcof1 mutants. However, the underlying mechanisms linking ribosome biogenesis and NCC development remain poorly understood. Here we report a new zebrafish mutant, fantome (fan), which harbors a point mutation and predicted premature stop codon in zebrafish wdr43, the ortholog to yeast UTP5. Although wdr43 mRNA is widely expressed during early zebrafish development, and its deficiency triggers early neural, eye, heart and pharyngeal arch defects, later defects appear fairly restricted to NCC derived craniofacial cartilages. Here we show that the C-terminus of Wdr43, which is absent in fan mutant protein, is both necessary and sufficient to mediate its nucleolar localization and protein interactions in metazoans. We demonstrate that Wdr43 functions in ribosome biogenesis, and that defects observed in fan mutants are mediated by a p53 dependent pathway. Finally, we show that proper localization of a variety of nucleolar proteins, including TCOF1, is dependent on that of WDR43. Together, our findings provide new insight into roles for Wdr43 in development, ribosome biogenesis, and also ribosomopathy-induced craniofacial phenotypes including Treacher-Collins Syndrome. PMID:24497835

[The main etiopathogenic mechanisms of neurocutaneous diseases].

PubMed

Vicente, F J; Gil, P; Vázquez-Doval, F J

1997-09-01

Neurocutaneous syndromes constitute a large and complex group of diseases in which recent medical advances, particularly in the field of molecular biology and genetics, have afforded a deeper understanding of the way in which these diseases originate. In this article, we review the advances concerning pathogenic mechanisms. First, we discuss the malformations disorders of the central nervous system associated with skin disorders, which range from spinal and/or cranial dysraphism with skin lesions to fustrated forms of malformations of the neural tube, such us membranous aplasia cutis. Neurocutaneous vascular disorders can be due to malformational disease, such as in Sturge-Weber syndrome, as well as to autoimmune diseases. The analysis of mutations affecting the capacity for migration and differentiation of melanocyte precursors enables us to gain a better understanding of disorders of the cells of the neural crest, such as piebaldism and Waardenburg's syndrome. Mutations in tumor suppressor genes play an important part in the development of hamartomatous and neoplastic lesions in neurofibromatosis and tuberous sclerosis. Genetic mosaicism, both of the functional and the genomic kind, accounts for the great diversity of phenotypes and the distribution of neurocutaneous diseases. Lastly, neurocutaneous syndromes such as the paracrinopathies form an attractive hypothesis, which is as yet to be confirmed.

Molecular and cellular biology of cerebral arteriovenous malformations: a review of current concepts and future trends in treatment.

PubMed

Rangel-Castilla, Leonardo; Russin, Jonathan J; Martinez-Del-Campo, Eduardo; Soriano-Baron, Hector; Spetzler, Robert F; Nakaji, Peter

2014-09-01

Arteriovenous malformations (AVMs) are classically described as congenital static lesions. However, in addition to rupturing, AVMs can undergo growth, remodeling, and regression. These phenomena are directly related to cellular, molecular, and physiological processes. Understanding these relationships is essential to direct future diagnostic and therapeutic strategies. The authors performed a search of the contemporary literature to review current information regarding the molecular and cellular biology of AVMs and how this biology will impact their potential future management. A PubMed search was performed using the key words "genetic," "molecular," "brain," "cerebral," "arteriovenous," "malformation," "rupture," "management," "embolization," and "radiosurgery." Only English-language papers were considered. The reference lists of all papers selected for full-text assessment were reviewed. Current concepts in genetic polymorphisms, growth factors, angiopoietins, apoptosis, endothelial cells, pathophysiology, clinical syndromes, medical treatment (including tetracycline and microRNA-18a), radiation therapy, endovascular embolization, and surgical treatment as they apply to AVMs are discussed. Understanding the complex cellular biology, physiology, hemodynamics, and flow-related phenomena of AVMs is critical for defining and predicting their behavior, developing novel drug treatments, and improving endovascular and surgical therapies.

Improving Visibility of Stereo-Radiographic Spine Reconstruction with Geometric Inferences.

PubMed

Kumar, Sampath; Nayak, K Prabhakar; Hareesha, K S

2016-04-01

Complex deformities of the spine, like scoliosis, are evaluated more precisely using stereo-radiographic 3D reconstruction techniques. Primarily, it uses six stereo-corresponding points available on the vertebral body for the 3D reconstruction of each vertebra. The wireframe structure obtained in this process has poor visualization, hence difficult to diagnose. In this paper, a novel method is proposed to improve the visibility of this wireframe structure using a deformation of a generic spine model in accordance with the 3D-reconstructed corresponding points. Then, the geometric inferences like vertebral orientations are automatically extracted from the radiographs to improve the visibility of the 3D model. Biplanar radiographs are acquired from five scoliotic subjects on a specifically designed calibration bench. The stereo-corresponding point reconstruction method is used to build six-point wireframe vertebral structures and thus the entire spine model. Using the 3D spine midline and automatically extracted vertebral orientation features, a more realistic 3D spine model is generated. To validate the method, the 3D spine model is back-projected on biplanar radiographs and the error difference is computed. Though, this difference is within the error limits available in the literature, the proposed work is simple and economical. The proposed method does not require more corresponding points and image features to improve the visibility of the model. Hence, it reduces the computational complexity. Expensive 3D digitizer and vertebral CT scan models are also excluded from this study. Thus, the visibility of stereo-corresponding point reconstruction is improved to obtain a low-cost spine model for a better diagnosis of spinal deformities.

Convergence of marine megafauna movement patterns in coastal and open oceans.

PubMed

Sequeira, A M M; Rodríguez, J P; Eguíluz, V M; Harcourt, R; Hindell, M; Sims, D W; Duarte, C M; Costa, D P; Fernández-Gracia, J; Ferreira, L C; Hays, G C; Heupel, M R; Meekan, M G; Aven, A; Bailleul, F; Baylis, A M M; Berumen, M L; Braun, C D; Burns, J; Caley, M J; Campbell, R; Carmichael, R H; Clua, E; Einoder, L D; Friedlaender, Ari; Goebel, M E; Goldsworthy, S D; Guinet, C; Gunn, J; Hamer, D; Hammerschlag, N; Hammill, M; Hückstädt, L A; Humphries, N E; Lea, M-A; Lowther, A; Mackay, A; McHuron, E; McKenzie, J; McLeay, L; McMahon, C R; Mengersen, K; Muelbert, M M C; Pagano, A M; Page, B; Queiroz, N; Robinson, P W; Shaffer, S A; Shivji, M; Skomal, G B; Thorrold, S R; Villegas-Amtmann, S; Weise, M; Wells, R; Wetherbee, B; Wiebkin, A; Wienecke, B; Thums, M

2018-03-20

The extent of increasing anthropogenic impacts on large marine vertebrates partly depends on the animals' movement patterns. Effective conservation requires identification of the key drivers of movement including intrinsic properties and extrinsic constraints associated with the dynamic nature of the environments the animals inhabit. However, the relative importance of intrinsic versus extrinsic factors remains elusive. We analyze a global dataset of ∼2.8 million locations from >2,600 tracked individuals across 50 marine vertebrates evolutionarily separated by millions of years and using different locomotion modes (fly, swim, walk/paddle). Strikingly, movement patterns show a remarkable convergence, being strongly conserved across species and independent of body length and mass, despite these traits ranging over 10 orders of magnitude among the species studied. This represents a fundamental difference between marine and terrestrial vertebrates not previously identified, likely linked to the reduced costs of locomotion in water. Movement patterns were primarily explained by the interaction between species-specific traits and the habitat(s) they move through, resulting in complex movement patterns when moving close to coasts compared with more predictable patterns when moving in open oceans. This distinct difference may be associated with greater complexity within coastal microhabitats, highlighting a critical role of preferred habitat in shaping marine vertebrate global movements. Efforts to develop understanding of the characteristics of vertebrate movement should consider the habitat(s) through which they move to identify how movement patterns will alter with forecasted severe ocean changes, such as reduced Arctic sea ice cover, sea level rise, and declining oxygen content.

Design and preliminary biomechanical analysis of artificial cervical joint complex.

PubMed

Jian, Yu; Lan-Tao, Liu; Zhao, Jian-ning; Jian-ning, Zhao

2013-06-01

To design an artificial cervical joint complex (ACJC) prosthesis for non-fusion reconstruction after cervical subtotal corpectomy, and to evaluate the biomechanical stability, preservation of segment movements and influence on adjacent inter-vertebral movements of this prosthesis. The prosthesis was composed of three parts: the upper/lower joint head and the middle artificial vertebrae made of Cobalt-Chromium-Molybdenum (Co-Cr-Mo) alloy and polyethylene with a ball-and-socket joint design resembling the multi-axial movement in normal inter-vertebral spaces. Biomechanical tests of intact spine (control), Orion locking plate system and ACJC prosthesis were performed on formalin-fixed cervical spine specimens from 21 healthy cadavers to compare stability, range of motion (ROM) of the surgical segment and ROM of adjacent inter-vertebral spaces. As for stability of the whole lower cervical spine, there was no significant difference of flexion, extension, lateral bending and torsion between intact spine group and ACJC prosthesis group. As for segment movements, difference in flexion, lateral bending or torsion between ACJC prosthesis group and control group was not statistically significant, while ACJC prosthesis group showed an increase in extension (P < 0.05) compared to that of the control group. In addition, ACJC prosthesis group demonstrated better flexion, extension and lateral bending compared to those of Orion plating system group (P < 0.05). Difference in adjacent inter-vertebral ROM of the ACJC prosthesis group was not statistically significant compared to that of the control group. After cervical subtotal corpectomy, reconstruction with ACJC prosthesis not only obtained instant stability, but also reserved segment motions effectively, without abnormal gain of mobility at adjacent inter-vertebral spaces.

Study of placenta of children born with congenital malformations.

PubMed

Stoll, Claude; Alembik, Yves; Dott, Béatrice; Roth, Marie-Paule

2003-01-01

The malformations in this study were observed in a series of 279,642 consecutive births of known outcome registered in our Registry of congenital anomalies. For each case, more than 50 factors included in the registration forms were studied. One of the factors studied was the placenta. For each malformed child, a control was chosen. Cases with maternal known factors impairing placenta function, i.e. vasculopathy and diabetes, were excluded. In each category of malformations studied, the malformed children were divided into isolated and non-isolated (multiple malformed) cases. The weight of placenta of isolated cases was not lower than the weight of placenta of the controls. In contrast, the weight of placenta of the cases with non-isolated malformations was lower than the weight of placenta of the controls and of the isolated cases, for all categories of malformations but gastroschisis and omphalocele. The mean weights at birth of the cases with multiple malformations were also lower than those of the controls. The human placenta discounts a principal functional part, the maternal blood in the intervillous space. Congenital malformations may interact with this function.

The MHC big bang.

PubMed

Abi Rached, L; McDermott, M F; Pontarotti, P

1999-02-01

The human Major Histocompatibility Complex (MHC) shares similarities with three other chromosome regions in human. This could be the vestige of ancestral large scale duplications. We discuss here the possibility i) that these duplications occurred during two rounds of tetraploidization supposed to have taken place during chordate evolution before the jawed vertebrate radiation, and ii) that one of the quadruplicate regions, relaxed of functional constraints, gave rise to the vertebrate MHC by a quick round of gene cis-duplication and cis-exon shuffling. These different rounds of cis-duplications and exon shufflings allowed the emergence of new genes participating in novel biological functions i.e. adaptive immune responses. Cis-duplications and cis-exon shufflings are ongoing processes in the evolution of some of these genes in this region as they have occurred and were fixed at different times and in different lineages during vertebrate evolution. In contrast, other genes within the MHC have remained stable since the emergence of jawed vertebrates.

New Perspectives on Pharyngeal Dorsoventral Patterning in Development and Evolution of the Vertebrate Jaw

PubMed Central

Medeiros, Daniel Meulemans; Crump, J. Gage

2012-01-01

Patterning of the vertebrate facial skeleton involves the progressive partitioning of neural-crest-derived skeletal precursors into distinct subpopulations along the anteroposterior (AP) and dorsoventral (DV) axes. Recent evidence suggests that complex interactions between multiple signaling pathways, in particular Endothelin-1 (Edn1), Bone Morphogenetic Protein (BMP), and Jagged-Notch, are needed to pattern skeletal precursors along the DV axis. Rather than directly determining the morphology of individual skeletal elements, these signals appear to act through several families of transcription factors, including Dlx, Msx, and Hand, to establish dynamic zones of skeletal differentiation. Provocatively, this patterning mechanism is largely conserved from mouse and zebrafish to the jawless vertebrate, lamprey. This implies that the diversification of the vertebrate facial skeleton, including the evolution of the jaw, was driven largely by modifications downstream of a conversed pharyngeal DV patterning program. PMID:22960284

Evolution and ecology of retinal photoreception in early vertebrates.

PubMed

Collin, Shaun P

2010-01-01

Visual ecology or the relationship between the visual system of an animal and its environment has proven to be a crucial research field for establishing general concepts of adaptation, specialization and evolution. The visual neuroscientist is indeed confronted with a plethora of different visual characteristics, each seemingly optimised for each species' ecological niche, but often without a clear understanding of the evolutionary constraints at play. However, before we are able to fully understand the influence(s) of ecology and phylogeny on visual system design in vertebrates, it is first necessary to understand the basic bauplan of key representatives of each taxa. This review examines photoreception in hagfishes, lampreys, cartilaginous fishes and lungfishes with an eye to their ecology using a range of neurobiological methods including anatomy, microspectrophotometry and molecular genetics. These early vertebrates represent critical stages in evolution and surprisingly possess a level of visual complexity that is almost unrivalled in other vertebrates. 2010 S. Karger AG, Basel.

Ultrasound-guided high-intensity focused ultrasound ablation for treating uterine arteriovenous malformation.

PubMed

Yan, X; Zhao, C; Tian, C; Wen, S; He, X; Zhou, Y

2017-08-01

To explore HIFU treatment for uterine arteriovenous malformation. A case report. Gynaecological department in a university teaching hospital of China. A patient with uterine arteriovenous malformation. The diagnosis of uterine arteriovenous malformation was made through MRI. Ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation was performed. HIFU is effective in treating uterine arteriovenous malformation. The patient had reduction of the lesion volume and obvious symptom relief, without significant adverse effects. HIFU can be used as a new treatment option for uterine arteriovenous malformation. Ultrasound-guided high-intensity focused ultrasound ablation is effective in treating uterine arteriovenous malformation. © 2017 Royal College of Obstetricians and Gynaecologists.

COMPARATIVE STUDY OF TUMORIGENESIS AND TUMOR IMMUNITY IN INVERTEBRATES AND NONMAMMALIAN VERTEBRATES

PubMed Central

Robert, Jacques

2010-01-01

Despite intense study in mammals, the different roles played by the immune system in detecting (immunosurveillance), controlling and remodeling (immunoediting) neoplasia, and perhaps in metastasis are not fully understood. In this review, I will present evidence of neoplasia and invasive malignancy, as well as tumor immunity in invertebrates and nonmammalian vertebrates. I will also present a comparative and evolutionary view of the complex interactions between neoplasia and the host immune system. Overall, I wish to go beyond the too simplistic dichotomy between invertebrates with innate immunity that are only affected with benign neoplasia and vertebrates with adaptive immunity that are affected by metastatic malignancies or cancer. PMID:20553753

Hind limb malformations in free-living northern leopard frogs (Rana pipiens) from Maine, Minnesota, and Vermont suggest multiple etiologies

USGS Publications Warehouse

Meteyer, C.U.; Loeffler, I.K.; Fallon, J.F.; Converse, K.A.; Green, E.; Helgen, J.C.; Kersten, S.; Levey, R.; Eaton-Poole, L.; Burkhart, J.G.

2000-01-01

Background Reports of malformed frogs have increased throughout the North American continent in recent years. Most of the observed malformations have involved the hind limbs. The goal of this study was to accurately characterize the hind limb malformations in wild frogs as an important step toward understanding the possible etiologies. Methods During 1997 and 1998, 182 recently metamorphosed northern leopard frogs (Rana pipiens) were collected from Minnesota, Vermont, and Maine. Malformed hind limbs were present in 157 (86%) of these frogs, which underwent necropsy and radiographic evaluation at the National Wildlife Health Center. These malformations are described in detail and classified into four major categories: (1) no limb (amelia); (2) multiple limbs or limb elements (polymelia, polydactyly, polyphalangy); (3) reduced limb segments or elements (phocomelia, ectromelia, ectrodactyly, and brachydactyly; and (4) distally complete but malformed limb (bone rotations, bridging, skin webbing, and micromelia). Results Amelia and reduced segments and/or elements were the most common finding. Frogs with bilateral hind limb malformations were not common, and in only eight of these 22 frogs were the malformations symmetrical. Malformations of a given type tended to occur in frogs collected from the same site, but the types of malformations varied widely among all three states, and between study sites within Minnesota. Conclusions Clustering of malformation type suggests that developmental events may produce a variety of phenotypes depending on the timing, sequence, and severity of the environmental insult. Hind limb malformations in free-living frogs transcend current mechanistic explanations of tetrapod limb development.

The pre-vertebrate origins of neurogenic placodes.

PubMed

Abitua, Philip Barron; Gainous, T Blair; Kaczmarczyk, Angela N; Winchell, Christopher J; Hudson, Clare; Kamata, Kaori; Nakagawa, Masashi; Tsuda, Motoyuki; Kusakabe, Takehiro G; Levine, Michael

2015-08-27

The sudden appearance of the neural crest and neurogenic placodes in early branching vertebrates has puzzled biologists for over a century. These embryonic tissues contribute to the development of the cranium and associated sensory organs, which were crucial for the evolution of the vertebrate "new head". A previous study suggests that rudimentary neural crest cells existed in ancestral chordates. However, the evolutionary origins of neurogenic placodes have remained obscure owing to a paucity of embryonic data from tunicates, the closest living relatives to those early vertebrates. Here we show that the tunicate Ciona intestinalis exhibits a proto-placodal ectoderm (PPE) that requires inhibition of bone morphogenetic protein (BMP) and expresses the key regulatory determinant Six1/2 and its co-factor Eya, a developmental process conserved across vertebrates. The Ciona PPE is shown to produce ciliated neurons that express genes for gonadotropin-releasing hormone (GnRH), a G-protein-coupled receptor for relaxin-3 (RXFP3) and a functional cyclic nucleotide-gated channel (CNGA), which suggests dual chemosensory and neurosecretory activities. These observations provide evidence that Ciona has a neurogenic proto-placode, which forms neurons that appear to be related to those derived from the olfactory placode and hypothalamic neurons of vertebrates. We discuss the possibility that the PPE-derived GnRH neurons of Ciona resemble an ancestral cell type, a progenitor to the complex neuronal circuit that integrates sensory information and neuroendocrine functions in vertebrates.

Staged corrective surgery for complex congenital scoliosis and split cord malformation

PubMed Central

Asad, Ambreen; Pasha, Ibrahim Farooq; Malik, Arslan Sharif; Arlet, Vincent

2009-01-01

Congenital scoliosis associated with split cord malformation raises the issue on how to best manage these patients to avoid neurologic injury while achieving satisfactory correction. We present the case of a 12-year-old girl who first presented when she was 11-year old with such combination but without much physical handicap or neurological deficit. The corrective surgery offered at that time was refused by the family. She again presented after 1 year with documented severe aggravation of the curve resulting in unstable walking and psychological upset. Her imaging studies showed multiple malformations in lower cervical and thoracic spine and a split cord malformation type 2 (fibrous septum with diplomyelia) at the apex of the deformity. A one-stage correction was deemed neurologically too risky. We therefore performed during a first stage a thoracotomy with anterior release. This was followed by skeletal traction with skull tongs and bilateral femoral pins. After gradual increase in traction weights a reasonable correction was achieved without any neurological deficit, over the next 10 days. A second-stage operation was done on the 11th day and a posterior instrumented fusion was performed. Post-operative recovery was uneventful and there were no complications. She was discharged with a Boston Brace to be worn for 3 months. At 2-year follow-up the patient outcome is excellent with excellent balance and correction of the deformity. In this grand round case, we discuss all the different option of treatment of congenital scoliosis associated with split cord malformation. In a medical environment where spinal cord monitoring is lacking, we recommend an initial release followed by skull and bifemoral traction over several days to monitor the neurologic status of the patient. Once optimal correction is achieved with the traction, a posterior instrumentation can be safely done. PMID:19626347

The African Turquoise Killifish: A Model for Exploring Vertebrate Aging and Diseases in the Fast Lane.

PubMed

Harel, Itamar; Brunet, Anne

2015-01-01

Why and how organisms age remains a mystery, and it defines one of the biggest challenges in biology. Aging is also the primary risk factor for many human pathologies, such as cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. Thus, manipulating the aging rate and potentially postponing the onset of these devastating diseases could have a tremendous impact on human health. Recent studies, relying primarily on nonvertebrate short-lived model systems, have shown the importance of both genetic and environmental factors in modulating the aging rate. However, relatively little is known about aging in vertebrates or what processes may be unique and specific to these complex organisms. Here we discuss how advances in genomics and genome editing have significantly expanded our ability to probe the aging process in a vertebrate system. We highlight recent findings from a naturally short-lived vertebrate, the African turquoise killifish, which provides an attractive platform for exploring mechanisms underlying vertebrate aging and age-related diseases. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Evolution of complex higher brain centers and behaviors: behavioral correlates of mushroom body elaboration in insects.

PubMed

Farris, Sarah M

2013-01-01

Large, complex higher brain centers have evolved many times independently within the vertebrates, but the selective pressures driving these acquisitions have been difficult to pinpoint. It is well established that sensory brain centers become larger and more structurally complex to accommodate processing of a particularly important sensory modality. When higher brain centers such as the cerebral cortex become greatly expanded in a particular lineage, it is likely to support the coordination and execution of more complex behaviors, such as those that require flexibility, learning, and social interaction, in response to selective pressures that made these new behaviors advantageous. Vertebrate studies have established a link between complex behaviors, particularly those associated with sociality, and evolutionary expansions of telencephalic higher brain centers. Enlarged higher brain centers have convergently evolved in groups such as the insects, in which multimodal integration and learning and memory centers called the mushroom bodies have become greatly elaborated in at least four independent lineages. Is it possible that similar selective pressures acting on equivalent behavioral outputs drove the evolution of large higher brain centers in all bilaterians? Sociality has greatly impacted brain evolution in vertebrates such as primates, but it has not been a major driver of higher brain center enlargement in insects. However, feeding behaviors requiring flexibility and learning are associated with large higher brain centers in both phyla. Selection for the ability to support behavioral flexibility appears to be a common thread underlying the evolution of large higher brain centers, but the precise nature of these computations and behaviors may vary. © 2013 S. Karger AG, Basel.

Safety and Efficacy Study of Sirolimus in Complicated Vascular Anomalies

ClinicalTrials.gov

2015-02-03

Kaposiform Hemangioendotheliomas; Tufted Angioma; Capillary Venous Lymphatic Malformation; Venous Lymphatic Malformation; Microcystic Lymphatic Malformation; Mucocutaneous Lymphangiomatosis and Thrombocytopenia; Capillary Lymphatic Arterial Venous Malformations; PTEN Overgrowth Syndrome With Vascular Anomaly; Lymphangiectasia Syndromes

Chiari Malformation

MedlinePlus

... Staying Safe Videos for Educators Search English Español Chiari Malformation KidsHealth / For Parents / Chiari Malformation What's in this ... balance problems, and other symptoms. What Is a Chiari Malformation? Normally, the cerebellum sits at the back of ...

Genome-wide Association Study for Radiographic Vertebral Fractures: A Potential Role for the 16q24 BMD Locus versus Lessons Learned from Challenging Phenotype Definition.

PubMed

Oei, Ling; Estrada, Karol; Duncan, Emma L; Christiansen, Claus; Liu, Ching-Ti; Langdahl, Bente L; Obermayer-Pietsch, Barbara; Riancho, José A; Prince, Richard L; van Schoor, Natasja M; McCloskey, Eugene; Hsu, Yi-Hsiang; Evangelou, Evangelos; Ntzani, Evangelia; Evans, David M; Alonso, Nerea; Husted, Lise B; Valero, Carmen; Hernandez, Jose L; Lewis, Joshua R; Kaptoge, Stephen K; Zhu, Kun; Cupples, L Adrienne; Medina-Gómez, Carolina; Vandenput, Liesbeth; Kim, Ghi Su; Lee, Seung Hun; Castaño-Betancourt, Martha C; Oei, Edwin H G; Martinez, Josefina; Daroszewska, Anna; van der Klift, Marjolein; Mellström, Dan; Herrera, Lizbeth; Karlsson, Magnus K; Hofman, Albert; Ljunggren, Osten; Pols, Huibert A P; Stolk, Lisette; van Meurs, Joyce B J; Ioannidis, John P A; Zillikens, M Carola; Lips, Paul; Karasik, David; Uitterlinden, André G; Styrkarsdottir, Unnur; Brown, Matthew A; Koh, Jung-Min; Richards, J Brent; Reeve, Jonathan; Ohlsson, Claes; Ralston, Stuart H; Kiel, Douglas P; Rivadeneira, Fernando

2013-10-25

Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2,666 controls with radiographic scoring (McCloskey-Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey-Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han-Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at P<5x10 -8 . In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p=4.6 x 10 -8 . However, the association was not significant across 5,720 cases and 21,791 controls from 14 studies. Fixed-effects meta analyses summary estimate was 1.06 (95% CI: 0.98-1.14; P=0.17), displaying high degree of heterogeneity (I 2 =57%; Qhet p= 0.0006). Under Han-Eskin alternative random effects model the summary effect was significant (P=0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size > 1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions are needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. © 2013.

Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus

PubMed Central

Oei, Ling; Estrada, Karol; Duncan, Emma L.; Christiansen, Claus; Liu, Ching-Ti; Langdahl, Bente L.; Obermayer-Pietsch, Barbara; Riancho, José A.; Prince, Richard L.; van Schoor, Natasja M.; McCloskey, Eugene; Hsu, Yi-Hsiang; Evangelou, Evangelos; Ntzani, Evangelia; Evans, David M.; Alonso, Nerea; Husted, Lise B.; Valero, Carmen; Hernandez, Jose L.; Lewis, Joshua R.; Kaptoge, Stephen K.; Zhu, Kun; Cupples, L. Adrienne; Medina-Gómez, Carolina; Vandenput, Liesbeth; Kim, Ghi Su; Lee, Seung Hun; Castaño-Betancourt, Martha C.; Oei, Edwin H.G.; Martinez, Josefina; Daroszewska, Anna; van der Klift, Marjolein; Mellström, Dan; Herrera, Lizbeth; Karlsson, Magnus K.; Hofman, Albert; Ljunggren, Östen; Pols, Huibert A.P.; Stolk, Lisette; van Meurs, Joyce B.J.; Ioannidis, John P.A.; Zillikens, M. Carola; Lips, Paul; Karasik, David; Uitterlinden, André G.; Styrkarsdottir, Unnur; Brown, Matthew A.; Koh, Jung-Min; Richards, J. Brent; Reeve, Jonathan; Ohlsson, Claes; Ralston, Stuart H.; Kiel, Douglas P.; Rivadeneira, Fernando

2014-01-01

Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p < 5 × 10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p=4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p = 0.17), displaying high degree of heterogeneity (I2=57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p = 0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. PMID:24516880

SOT Risk Assessment: Complex mixtures of anti-androgens at concentrations below individual chemical effect levels produces reproductive tract malformations in the male rat

EPA Science Inventory

This product is an invited webinar to the Society of Toxicology Risk Assessment Specialty Section (co-hosted by the Mixtures Specialty Section) as part of their monthly webinar series. The webinar is scheduled for 3:00PM on Wednesday September 13th.

Zebrafish and relational memory: Could a simple fish be useful for the analysis of biological mechanisms of complex vertebrate learning?

PubMed

Gerlai, Robert

2017-08-01

Analysis of the zebrafish allows one to combine two distinct scientific approaches, comparative ethology and neurobehavioral genetics. Furthermore, this species arguably represents an optimal compromise between system complexity and practical simplicity. This mini-review focuses on a complex form of learning, relational learning and memory, in zebrafish. It argues that zebrafish are capable of this type of learning, and it attempts to show how this species may be useful in the analysis of the mechanisms and the evolution of this complex brain function. The review is not intended to be comprehensive. It is a short opinion piece that reflects the author's own biases, and it draws some of its examples from the work coming from his own laboratory. Nevertheless, it is written in the hope that it will persuade those who have not utilized zebrafish and who may be interested in opening their research horizon to this relatively novel but powerful vertebrate research tool. Copyright © 2017 Elsevier B.V. All rights reserved.

Getting to the core of cadherin complex function in Caenorhabditis elegans.

PubMed

Hardin, Jeff

2015-01-01

The classic cadherin-catenin complex (CCC) mediates cell-cell adhesion in metazoans. Although substantial insights have been gained by studying the CCC in vertebrate tissue culture, analyzing requirements for and regulation of the CCC in vertebrates remains challenging. Caenorhabditis elegans is a powerful system for connecting the molecular details of CCC function with functional requirements in a living organism. Recent data, using an "angstroms to embryos" approach, have elucidated functions for key residues, conserved across all metazoans, that mediate cadherin/β-catenin binding. Other recent work reveals a novel, potentially ancestral, role for the C. elegans p120ctn homologue in regulating polarization of blastomeres in the early embryo via Cdc42 and the partitioning-defective (PAR)/atypical protein kinase C (aPKC) complex. Finally, recent work suggests that the CCC is trafficked to the cell surface via the clathrin adaptor protein complex 1 (AP-1) in surprising ways. These studies continue to underscore the value of C. elegans as a model system for identifying conserved molecular mechanisms involving the CCC.

Structural Basis and Function of XRN2-Binding by XTB Domains

PubMed Central

Richter, Hannes; Katic, Iskra; Gut, Heinz; Großhans, Helge

2016-01-01

The ribonuclease XRN2 is an essential player in RNA metabolism. In Caenorhabditis elegans, XRN2 functions with PAXT-1, which shares a putative XRN2-binding domain (XTBD) with otherwise unrelated mammalian proteins. Here, we characterize structure and function of an XTBD – XRN2 complex. Although XTBD stably interconnects two XRN2 domains through numerous interacting residues, mutation of a single critical residue suffices to disrupt XTBD – XRN2 complexes in vitro, and recapitulates paxt-1 null mutant phenotypes in vivo. Demonstrating conservation of function, vertebrate XTBD-containing proteins bind XRN2 in vitro, and human CDKN2AIPNL (C2AIL) can substitute for PAXT-1 in vivo. In vertebrates, where three distinct XTBD-containing proteins exist, XRN2 may partition to distinct stable heterodimeric complexes, likely differing in subcellular localization or function. In C. elegans, complex formation with the unique PAXT-1 serves to preserve the stability of XRN2 in the absence of substrate. PMID:26779609

Color-coded perfusion analysis of CEUS for pre-interventional diagnosis of microvascularisation in cases of vascular malformations.

PubMed

Teusch, V I; Wohlgemuth, W A; Piehler, A P; Jung, E M

2014-01-01

Aim of our pilot study was the application of a contrast-enhanced color-coded ultrasound perfusion analysis in patients with vascular malformations to quantify microcirculatory alterations. 28 patients (16 female, 12 male, mean age 24.9 years) with high flow (n = 6) or slow-flow (n = 22) malformations were analyzed before intervention. An experienced examiner performed a color-coded Doppler sonography (CCDS) and a Power Doppler as well as a contrast-enhanced ultrasound after intravenous bolus injection of 1 - 2.4 ml of a second-generation ultrasound contrast medium (SonoVue®, Bracco, Milan). The contrast-enhanced examination was documented as a cine sequence over 60 s. The quantitative analysis based on color-coded contrast-enhanced ultrasound (CEUS) images included percentage peak enhancement (%peak), time to peak (TTP), area under the curve (AUC), and mean transit time (MTT). No side effects occurred after intravenous contrast injection. The mean %peak in arteriovenous malformations was almost twice as high as in slow-flow-malformations. The area under the curve was 4 times higher in arteriovenous malformations compared to the mean value of other malformations. The mean transit time was 1.4 times higher in high-flow-malformations compared to slow-flow-malformations. There was no difference regarding the time to peak between the different malformation types. The comparison between all vascular malformation and surrounding tissue showed statistically significant differences for all analyzed data (%peak, TTP, AUC, MTT; p < 0.01). High-flow and slow-flow vascular malformations had statistically significant differences in %peak (p < 0.01), AUC analysis (p < 0.01), and MTT (p < 0.05). Color-coded perfusion analysis of CEUS seems to be a promising technique for the dynamic assessment of microvasculature in vascular malformations.

Epilepsy in the setting of full trisomy 18: A multicenter study on 18 affected children with and without structural brain abnormalities.

PubMed

Matricardi, Sara; Spalice, Alberto; Salpietro, Vincenzo; Di Rosa, Gabriella; Balistreri, Maria Cristina; Grosso, Salvatore; Parisi, Pasquale; Elia, Maurizio; Striano, Pasquale; Accorsi, Patrizia; Cusmai, Raffaella; Specchio, Nicola; Coppola, Giangennaro; Savasta, Salvatore; Carotenuto, Marco; Tozzi, Elisabetta; Ferrara, Pietro; Ruggieri, Martino; Verrotti, Alberto

2016-09-01

This paper reports on the clinical aspects, electroencephalographic (EEG) features, and neuroimaging findings in children with full trisomy 18 and associated epilepsy, and compares the evolution and outcome of their neurological phenotype. We retrospectively studied 18 patients (10 males and 8 females; aged 14 months to 9 years) with full trisomy 18 and epilepsy. All patients underwent comprehensive assessment including neuroimaging studies of the brain. We divided patients into two groups according to neuroimaging findings: (Group 1) 10 patients harboring structural brain malformations, and (Group 2) 8 patients with normal brain images. Group 1 had a significantly earlier age at seizure onset (2 months) compared to Group 2 (21 months). The seizure semiology was more severe in Group 1, who presented multiple seizure types, need for polytherapy (80% of patients), multifocal EEG abnormalities and poorer outcome (drug resistant epilepsy in 90% of patients) than Group 2 who presented a single seizure type, generalized or focal, and non-specific EEG pattern; these patients were successfully treated with monotherapy with good outcome. Imaging revealed a wide and complex spectrum of structural brain abnormalities including anomalies of the commissures, cerebellar malformations, cortical abnormalities, and various degrees of cortical atrophy. Epilepsy in full trisomy 18 may develop during the first months of life and can be associated with structural brain malformations. Patients with brain malformations can show multiple seizure types and can frequently be resistant to therapy with antiepileptic drugs. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Regulation of early Xenopus development by ErbB signaling

PubMed Central

Nie, Shuyi; Chang, Chenbei

2008-01-01

ErbB signaling has long been implicated in cancer formation and progression and is shown to regulate cell division, migration and death during tumorigenesis. The functions of the ErbB pathway during early vertebrate embryogenesis, however, are not well understood. Here we report characterization of ErbB activities during early frog development. Gain-of-function analyses show that EGFR, ErbB2 and ErbB4 induce ectopic tumor-like cell mass that contains increased numbers of mitotic cells. Both the muscle and the neural markers are expressed in these ectopic protrusions. ErbBs also induce mesodermal markers in ectodermal explants. Loss-of-function studies using carboxyl terminal-truncated dominant-negative ErbB receptors demonstrate that blocking ErbB signals leads to defective gastrulation movements and malformation of the embryonic axis with a reduction in the head structures in early frog embryos. These data, together with the observation that ErbBs are expressed early during frog embryogenesis, suggest that ErbBs regulate cell proliferation, movements and embryonic patterning during early Xenopus development. PMID:16258939

cis-Regulatory Mutations Are a Genetic Cause of Human Limb Malformations

PubMed Central

VanderMeer, Julia E.; Ahituv, Nadav

2011-01-01

The underlying mutations that cause human limb malformations are often difficult to determine, particularly for limb malformations that occur as isolated traits. Evidence from a variety of studies shows that cis-regulatory mutations, specifically in enhancers, can lead to some of these isolated limb malformations. Here, we provide a review of human limb malformations that have been shown to be caused by enhancer mutations and propose that cis-regulatory mutations will continue to be identified as the cause of additional human malformations as our understanding of regulatory sequences improves. PMID:21509892

Evolution of an RNP assembly system: A minimal SMN complex facilitates formation of UsnRNPs in Drosophila melanogaster

PubMed Central

Kroiss, Matthias; Schultz, Jörg; Wiesner, Julia; Chari, Ashwin; Sickmann, Albert; Fischer, Utz

2008-01-01

In vertebrates, assembly of spliceosomal uridine-rich small nuclear ribonucleoproteins (UsnRNPs) is mediated by the SMN complex, a macromolecular entity composed of the proteins SMN and Gemins 2–8. Here we have studied the evolution of this machinery using complete genome assemblies of multiple model organisms. The SMN complex has gained complexity in evolution by a blockwise addition of Gemins onto an ancestral core complex composed of SMN and Gemin2. In contrast to this overall evolutionary trend to more complexity in metazoans, orthologs of most Gemins are missing in dipterans. In accordance with these bioinformatic data a previously undescribed biochemical purification strategy elucidated that the dipteran Drosophila melanogaster contains an SMN complex of remarkable simplicity. Surprisingly, this minimal complex not only mediates the assembly reaction in a manner very similar to its vertebrate counterpart, but also prevents misassembly onto nontarget RNAs. Our data suggest that only a minority of Gemins are required for the assembly reaction per se, whereas others may serve additional functions in the context of UsnRNP biogenesis. The evolution of the SMN complex is an interesting example of how the simplification of a biochemical process contributes to genome compaction. PMID:18621711

Prevalence of skeletal and eye malformations in frogs from north-central United States: estimations based on collections from randomly selected sites.

PubMed

Schoff, Patrick K; Johnson, Catherine M; Schotthoefer, Anna M; Murphy, Joseph E; Lieske, Camilla; Cole, Rebecca A; Johnson, Lucinda B; Beasley, Val R

2003-07-01

Skeletal malformation rates for several frog species were determined in a set of randomly selected wetlands in the north-central USA over three consecutive years. In 1998, 62 sites yielded 389 metamorphic frogs, nine (2.3%) of which had skeletal or eye malformations. A subset of the original sites was surveyed in the following 2 yr. In 1999, 1,085 metamorphic frogs were collected from 36 sites and 17 (1.6%) had skeletal or eye malformations, while in 2000, examination of 1,131 metamorphs yielded 16 (1.4%) with skeletal or eye malformations. Hindlimb malformations predominated in all three years, but other abnormalities, involving forelimb, eye, and pelvis were also found. Northern leopard frogs (Rana pipiens) constituted the majority of collected metamorphs as well as most of the malformed specimens. However, malformations were also noted in mink frogs (R. septentrionalis), wood frogs (R. sylvatica), and gray tree frogs (Hyla spp.). The malformed specimens were found in clustered sites in all three years but the cluster locations were not the same in any year. The malformation rates reported here are higher than the 0.3% rate determined for metamorphic frogs collected from similar sites in Minnesota in the 1960s, and thus, appear to represent an elevation of an earlier baseline malformation rate.

Prevalence of skeletal and eye malformations in frogs from north-central United States: estimations based on collections from randomly selected sites

USGS Publications Warehouse

Schoff, P.K.; Johnson, C.M.; Schotthoefer, A.M.; Murphy, J.E.; Lieske, C.; Cole, Rebecca A.; Johnson, L.B.; Beasley, V.R.

2003-01-01

Skeletal malformation rates for several frog species were determined in a set of randomly selected wetlands in the north-central USA over three consecutive years. In 1998, 62 sites yielded 389 metamorphic frogs, nine (2.3%) of which had skeletal or eye malformations. A subset of the original sites was surveyed in the following 2 yr. In 1999, 1,085 metamorphic frogs were collected from 36 sites and 17 (1.6%) had skeletal or eye malformations, while in 2000, examination of 1,131 metamorphs yielded 16 (1.4%) with skeletal or eye malformations. Hindlimb malformations predominated in all three years, but other abnormalities, involving forelimb, eye, and pelvis were also found. Northern leopard frogs (Rana pipiens) constituted the majority of collected metamorphs as well as most of the malformed specimens. However, malformations were also noted in mink frogs (R. septentrionalis), wood frogs (R. sylvatica), and gray tree frogs (Hyla spp.). The malformed specimens were found in clustered sites in all three years but the cluster locations were not the same in any year. The malformation rates reported here are higher than the 0.3% rate determined for metamorphic frogs collected from similar sites in Minnesota in the 1960s, and thus, appear to represent an elevation of an earlier baseline malformation rate.

Lessons from Amphioxus Bauplan About Origin of Cranial Nerves of Vertebrates That Innervates Extrinsic Eye Muscles.

PubMed

Ferran, José Luis; Puelles, Luis

2018-04-16

Amphioxus is the living chordate closest to the ancestral form of vertebrates, and in a key position to reveal essential aspects of the evolution of the brain Bauplan of vertebrates. The dorsal neural cord of this species at the larval stage is characterized by a small cerebral vesicle at its anterior end and a large posterior region. The latter is comparable in some aspects to the hindbrain and spinal cord regions of vertebrates. The rostral end of the cerebral vesicle contains a median pigment spot and associated rows of photoreceptor and other nerve cells; this complex is known as "the frontal eye." However, this is not a complete eye in the sense that it has neither eye muscles nor lens (only a primitive retina-like tissue). Cranial nerves III, IV, and VI take part in the motor control of eye muscles in all vertebrates. Using a recent model that postulates distinct molecularly characterized hypothalamo-prethalamic and mesodiencephalic domains in the early cerebral vesicle of amphioxus, we analyze here possible scenarios for the origin from the common ancestor of cephalochordates and vertebrates of the cranial nerves related with extrinsic eye muscle innervations. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Unusual anal fin in a Devonian jawless vertebrate reveals complex origins of paired appendages

PubMed Central

Sansom, Robert S.; Gabbott, Sarah E.; Purnell, M. A.

2013-01-01

Jawed vertebrates (gnathostomes) have undergone radical anatomical and developmental changes in comparison with their jawless cousins (cyclostomes). Key among these is paired appendages (fins, legs and wings), which first evolved at some point on the gnathostome stem. The anatomy of fossil stem gnathostomes is, therefore, fundamental to our understanding of the nature and timing of the origin of this complex innovation. Here, we show that Euphanerops, a fossil jawless fish from the Devonian, possessed paired anal-fin radials, but no pectoral or pelvic fins. This unique condition occurs at an early stage on the stem-gnathostome lineage. This condition, and comparison with the varied condition of paired fins in other ostracoderms, indicates that there was a large amount of developmental plasticity during this episode—rather than a gradual evolution of this complex feature. Apparently, a number of different clades were exploring morphospace or undergoing multiple losses. PMID:23576777

Arteriovenous malformation of the vulva: a case report.

PubMed

Pereira, Nigel; Dormosh, Mayes; Mirmanesh, Michael; Guilfoil, Daniel S

2014-01-01

To report the case of a patient with a large and symptomatic vulvar lesion, necessitating surgical excision. We report the case of a 57-year-old postmenopausal woman with a 6-month history of an enlarging vulvar lesion associated with vulvar pruritus. On examination, a pedunculated 7 × 5 × 4-cm soft tissue mass attached to the left labium majus was noted. Surgical excision was performed and histopathologic evaluation revealed variably dilated, submucosal vessels with thick muscular walls and intimal thickening, but without endothelial atypia or multilayering. These findings were consistent with a final diagnosis of arteriovenous malformation of the vulva. Given the complex anatomy of the vulva, the differential diagnosis for vulvar vascular lesions can be challenging. Hence, surgical excision and histopathologic evaluation become imperative to distinguish them from other dermatologic and neoplastic conditions of the vulva.

Ancient duplications and functional divergence in the interferon regulatory factors of vertebrates provide insights into the evolution of vertebrate immune systems.

PubMed

Du, Kang; Zhong, Zaixuan; Fang, Chengchi; Dai, Wei; Shen, Yanjun; Gan, Xiaoni; He, Shunping

2018-04-01

Interferon regulatory factors (IRFs) were first discovered as transcription factors that regulate the transcription of human interferon (IFN)-β. Increasing evidence shows that they might be important players involved in Adaptive immune system (AIS) evolution. Although numbers of IRFs have been identified in chordates, the evolutionary history and functional diversity of this gene family during the early evolution of vertebrates have remained obscure. Using IRF HMM profile and HMMER searches, we identified 148 IRFs in 11 vertebrates and 4 protochordates. For them, we reconstructed the phylogenetic relationships, determined the synteny conservation, investigated the profile of natural selection, and analyzed the expression patterns in four "living fossil" vertebrates: lamprey, elephant shark, coelacanth and bichir. The results from phylogeny and synteny analysis imply that vertebrate IRFs evolved from three predecessors, instead of four as suggested in a previous study, as results from an ancient duplication followed by special expansions and lost during the vertebrate evolution. The profile of natural selection and expression reveals functional dynamics during the process. Together, they suggest that the 2nd whole-genome duplication (2WGD) provided raw materials for innovation in the IRF family, and that the birth of type-I IFN might be an important factor inducing the establishment of IRF-mediated immune networks. As a member involved in the AIS evolution, IRF provide insights into the process and mechanism involved in the complexity and novelties of vertebrate immune systems. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Whole Genome Duplications Shaped the Receptor Tyrosine Kinase Repertoire of Jawed Vertebrates

PubMed Central

Brunet, Frédéric G.; Volff, Jean-Nicolas; Schartl, Manfred

2016-01-01

The receptor tyrosine kinase (RTK) gene family, involved primarily in cell growth and differentiation, comprises proteins with a common enzymatic tyrosine kinase intracellular domain adjacent to a transmembrane region. The amino-terminal portion of RTKs is extracellular and made of different domains, the combination of which characterizes each of the 20 RTK subfamilies among mammals. We analyzed a total of 7,376 RTK sequences among 143 vertebrate species to provide here the first comprehensive census of the jawed vertebrate repertoire. We ascertained the 58 genes previously described in the human and mouse genomes and established their phylogenetic relationships. We also identified five additional RTKs amounting to a total of 63 genes in jawed vertebrates. We found that the vertebrate RTK gene family has been shaped by the two successive rounds of whole genome duplications (WGD) called 1R and 2R (1R/2R) that occurred at the base of the vertebrates. In addition, the Vegfr and Ephrin receptor subfamilies were expanded by single gene duplications. In teleost fish, 23 additional RTK genes have been retained after another expansion through the fish-specific third round (3R) of WGD. Several lineage-specific gene losses were observed. For instance, birds have lost three RTKs, and different genes are missing in several fish sublineages. The RTK gene family presents an unusual high gene retention rate from the vertebrate WGDs (58.75% after 1R/2R, 64.4% after 3R), resulting in an expansion that might be correlated with the evolution of complexity of vertebrate cellular communication and intracellular signaling. PMID:27260203

Vascular lumen formation.

PubMed

Lammert, Eckhard; Axnick, Jennifer

2012-04-01

The vascular system developed early in evolution. It is required in large multicellular organisms for the transport of nutrients, oxygen, and waste products to and from tissues. The vascular system is composed of hollow tubes, which have a high level of complexity in vertebrates. Vasculogenesis describes the de novo formation of blood vessels, e.g., aorta formation in vertebrate embryogenesis. In contrast, angiogenesis is the formation of blood vessels from preexisting ones, e.g., sprouting of intersomitic blood vessels from the aorta. Importantly, the lumen of all blood vessels in vertebrates is lined and formed by endothelial cells. In both vasculogenesis and angiogenesis, lumen formation takes place in a cord of endothelial cells. It involves a complex molecular mechanism composed of endothelial cell repulsion at the cell-cell contacts within the endothelial cell cords, junctional rearrangement, and endothelial cell shape change. As the vascular system also participates in the course of many diseases, such as cancer, stroke, and myocardial infarction, it is important to understand and make use of the molecular mechanisms of blood vessel formation to better understand and manipulate the pathomechanisms involved.

Fish pigmentation and the melanocortin system.

PubMed

Cal, Laura; Suarez-Bregua, Paula; Cerdá-Reverter, José Miguel; Braasch, Ingo; Rotllant, Josep

2017-09-01

The melanocortin system is a complex neuroendocrine signaling mechanism involved in numerous physiological processes in vertebrates, including pigmentation, steroidogenesis and metabolic control. This review focuses at one of its most fascinating function in fish, its regulatory role in the control of pigmentation, in which the melanocortin 1 receptor (Mc1r), its agonist α-melanocyte stimulating hormone (α-Msh), and the endogenous antagonist agouti signaling protein (Asip1) are the main players. Functional control of Mc1r, which is highly expressed in fish skin and whose activation stimulates melanin production and melanosome dispersion in fish melanophores, is considered a key mechanism for vertebrate pigment phenotypes. The α-Msh peptide, the most documented Mc1r agonist involved in pigmentation, is produced in the pituitary gland, activating melanin synthesis by binding to Mc1r in fish melanophores. Finally, Asip1 is the putative factor for establishing the evolutionarily conserved dorso-ventral pigment pattern found across vertebrates. However, we are just starting to understand how other melanocortin system components are acting in this complex regulatory network. Copyright © 2017 Elsevier Inc. All rights reserved.

The paranasal sinuses: the last frontier in craniofacial biology.

PubMed

Márquez, Samuel

2008-11-01

This special issue of the Anatomical Record explores the presence and diversity of paranasal sinuses in distinct vertebrate groups. The following topics are addressed in particular: dinosaur physiology; development; physiology; adaptation; imaging; and primate systematics. A variety of approaches and techniques are used to examine and characterize the diversity of paranasal sinus pneumatization in a wide spectrum of vertebrates. These range from dissection to histology, from plain X-rays to computer tomography, from comparative anatomy to natural experimental settings, from mathematical computation to computer model simulation, and 2D to 3D reconstructions. The articles in this issue are a combination of literature review and new, hypothesis-driven anatomical research that highlights the complexities of paranasal sinus growth and development; ontogenetic and disease processes; physiology; paleontology; primate systematics; and human evolution. The issue incorporates a wide variety of vertebrates, encompassing a period of over 65 million years, in an effort to offer insight into the diversity of the paranasal sinus complexes through time and space, and thereby providing a greater understanding and appreciation of these special spaces within the cranium. Copyright 2008 Wiley-Liss, Inc.

COMPLEX EVOLUTION OF BILE SALTS IN BIRDS

PubMed Central

Hagey, Lee R.; Vidal, Nicolas; Hofmann, Alan F.; Krasowski, Matthew D.

2010-01-01

Bile salts are the major end-metabolites of cholesterol and are important in lipid digestion and shaping of the gut microflora. There have been limited studies of bile-salt variation in birds. The purpose of our study was to determine bile-salt variation among birds and relate this variation to current avian phylogenies and hypotheses on the evolution of bile salt pathways. We determined the biliary bile-salt composition of 405 phylogenetically diverse bird species, including 7 paleognath species. Bile salt profiles were generally stable within bird families. Complex bile-salt profiles were more common in omnivores and herbivores than in carnivores. The structural variation of bile salts in birds is extensive and comparable to that seen in surveys of bile salts in reptiles and mammals. Birds produce many of the bile salts found throughout nonavian vertebrates and some previously uncharacterized bile salts. One difference between birds and other vertebrates is extensive hydroxylation of carbon-16 of bile salts in bird species. Comparison of our data set of bird bile salts with that of other vertebrates, especially reptiles, allowed us to infer evolutionary changes in the bile salt synthetic pathway. PMID:21113274

Plant nuclear pore complex proteins are modified by novel oligosaccharides with terminal N-acetylglucosamine.

PubMed Central

Heese-Peck, A; Cole, R N; Borkhsenious, O N; Hart, G W; Raikhel, N V

1995-01-01

Only a few nuclear pore complex (NPC) proteins, mainly in vertebrates and yeast but none in plants, have been well characterized. As an initial step to identify plant NPC proteins, we examined whether NPC proteins from tobacco are modified by N-acetylglucosamine (GlcNAc). Using wheat germ agglutinin, a lectin that binds specifically to GlcNAc in plants, specific labeling was often found associated with or adjacent to NPCs. Nuclear proteins containing GlcNAc can be partially extracted by 0.5 M salt, as shown by a wheat germ agglutinin blot assay, and at least eight extracted proteins were modified by terminal GlcNAc, as determined by in vitro galactosyltransferase assays. Sugar analysis indicated that the plant glycans with terminal GlcNAc differ from the single O-linked GlcNAc of vertebrate NPC proteins in that they consist of oligosaccharides that are larger in size than five GlcNAc residues. Most of these appear to be bound to proteins via a hydroxyl group. This novel oligosaccharide modification may convey properties to the plant NPC that are different from those of vertebrate NPCs. PMID:8589629

Field guide to malformations of frogs and toads: with radiographic interpretations

USGS Publications Warehouse

Meteyer, Carol U.

2000-01-01

In 1995, students found numerous malformed frogs on a field trip to a Minnesota pond. Since that time, reports of malformed frogs have increased dramatically. Malformed frogs have now been reported in 44 states in 38 species of frogs, and 19 species of toads. Estimates as high as 60% of the newly metamorphosed frog populations have had malformations at some ponds (NARCAM, ’99). The wide geographic distribution of malformed frogs and the variety of malformations are a concern to resource managers, research scientists and public health officials. The potential for malformations to serve as a signal of ecosystem disruption, and the affect this potential disruption might have on other organisms that share those ecosystems, has not been resolved. Malformations represent an error that occurred early in development. The event that caused the developmental error is temporally distant from the malformation we see in the fully developed animal. Knowledge of normal developmental principles is necessary to design thoughtful investigations that will define the events involved in abnormal development in wild frog populations.Development begins at the time an egg is fertilized and progresses by chemical communication between cells and cell layers. This communication is programmed through gene expression. Malformations represent primary errors in development, errors in chemical communication or translation of genetic information. Deformations arise later in development and usually result from the influence of mechanical factors (such as amputation) that alter shape or anatomy of a structure that has developed normally. The occurrence and the type of malformations are influenced by the type of error or insult as well as the timing of the error (the developmental stage at which the error occurred). The appearance of the malformation can therefore provide clues that suggest when the error may have occurred. If the malformation is an incomplete organ, such as an incomplete limb, the factor or insult acted during a susceptible period prior to organ completion. Although defining the anatomy of the malformed metamorphosed frog can give us an idea of the approximate window during which the developmental insult was initiated, and might even suggest the type of insult that may have occurred, the morphology of the malformation does not define the cause. To define causes and mechanisms of frog malformations we need to use well designed investigations that are different from traditional tests used in acute toxicity or disease pathogenicity studies. When investigating malformations in metamorphosed frogs, we are looking at the affect of exposure to an agent that occurred early in tadpole development. Therefore investigations to determine causes of malformations need to look at agents that are present in the tadpoles or their environments at these early developmental times. Laboratory experiments need to expose embryos and tadpoles to suspect agents at appropriate developmental stages and look at acute results, such as toxicity and death, as well as following the developmental process to completion to determine the impact of the agent on the developing tadpole and the fully developed frog. This means holding animals past metamorphic climax to assure that the anatomy and physiology of the adult have developed normally.As we look at field collections of abnormal frogs, we need to keep in mind that these collections reflect survivors only. We are looking at malformations that were not fatal to tadpoles. We cannot assume that because we do not collect other malformations, they did not exist. More work needs to be done on the developing tadpole, in the field and in the laboratory, to better elucidate the range, frequency, character and causes of anuran malformations.

Host Range Restriction of Insect-Specific Flaviviruses Occurs at Several Levels of the Viral Life Cycle.

PubMed

Junglen, Sandra; Korries, Marvin; Grasse, Wolfgang; Wieseler, Janett; Kopp, Anne; Hermanns, Kyra; León-Juárez, Moises; Drosten, Christian; Kümmerer, Beate Mareike

2017-01-01

The genus Flavivirus contains emerging arthropod-borne viruses (arboviruses) infecting vertebrates, as well as insect-specific viruses (ISVs) (i.e., viruses whose host range is restricted to insects). ISVs are evolutionary precursors to arboviruses. Knowledge of the nature of the ISV infection block in vertebrates could identify functions necessary for the expansion of the host range toward vertebrates. Mapping of host restrictions by complementation of ISV and arbovirus genome functions could generate knowledge critical to predicting arbovirus emergence. Here we isolated a novel flavivirus, termed Niénokoué virus (NIEV), from mosquitoes sampled in Côte d'Ivoire. NIEV groups with insect-specific flaviviruses (ISFs) in phylogeny and grows in insect cells but not in vertebrate cells. We generated an infectious NIEV cDNA clone and a NIEV reporter replicon to study growth restrictions of NIEV in comparison to yellow fever virus (YFV), for which the same tools are available. Efficient RNA replication of the NIEV reporter replicon was observed in insect cells but not in vertebrate cells. Initial translation of the input replicon RNA in vertebrate cells was functional, but RNA replication did not occur. Chimeric YFV carrying the envelope proteins of NIEV was recovered via electroporation in C6/36 insect cells but did not infect vertebrate cells, indicating a block at the level of entry. Since the YF/NIEV chimera readily produced infectious particles in insect cells but not in vertebrate cells despite efficient RNA replication, restriction is also determined at the level of assembly/release. Taking the results together, the ability of ISF to infect vertebrates is blocked at several levels, including attachment/entry and RNA replication as well as assembly/release. IMPORTANCE Most viruses of the genus Flavivirus , e.g., YFV and dengue virus, are mosquito borne and transmitted to vertebrates during blood feeding of mosquitoes. Within the last decade, an increasing number of viruses with a host range exclusively restricted to insects in close relationship to the vertebrate-pathogenic flaviviruses were discovered in mosquitoes. To identify barriers that could block the arboviral vertebrate tropism, we set out to identify the steps at which the ISF replication cycle fails in vertebrates. Our studies revealed blocks at several levels, suggesting that flavivirus host range expansion from insects to vertebrates was a complex process that involved overcoming multiple barriers.

Host Range Restriction of Insect-Specific Flaviviruses Occurs at Several Levels of the Viral Life Cycle

PubMed Central

Junglen, Sandra; Korries, Marvin; Grasse, Wolfgang; Wieseler, Janett; Kopp, Anne; Hermanns, Kyra; León-Juárez, Moises; Drosten, Christian

2017-01-01

ABSTRACT The genus Flavivirus contains emerging arthropod-borne viruses (arboviruses) infecting vertebrates, as well as insect-specific viruses (ISVs) (i.e., viruses whose host range is restricted to insects). ISVs are evolutionary precursors to arboviruses. Knowledge of the nature of the ISV infection block in vertebrates could identify functions necessary for the expansion of the host range toward vertebrates. Mapping of host restrictions by complementation of ISV and arbovirus genome functions could generate knowledge critical to predicting arbovirus emergence. Here we isolated a novel flavivirus, termed Niénokoué virus (NIEV), from mosquitoes sampled in Côte d’Ivoire. NIEV groups with insect-specific flaviviruses (ISFs) in phylogeny and grows in insect cells but not in vertebrate cells. We generated an infectious NIEV cDNA clone and a NIEV reporter replicon to study growth restrictions of NIEV in comparison to yellow fever virus (YFV), for which the same tools are available. Efficient RNA replication of the NIEV reporter replicon was observed in insect cells but not in vertebrate cells. Initial translation of the input replicon RNA in vertebrate cells was functional, but RNA replication did not occur. Chimeric YFV carrying the envelope proteins of NIEV was recovered via electroporation in C6/36 insect cells but did not infect vertebrate cells, indicating a block at the level of entry. Since the YF/NIEV chimera readily produced infectious particles in insect cells but not in vertebrate cells despite efficient RNA replication, restriction is also determined at the level of assembly/release. Taking the results together, the ability of ISF to infect vertebrates is blocked at several levels, including attachment/entry and RNA replication as well as assembly/release. IMPORTANCE Most viruses of the genus Flavivirus, e.g., YFV and dengue virus, are mosquito borne and transmitted to vertebrates during blood feeding of mosquitoes. Within the last decade, an increasing number of viruses with a host range exclusively restricted to insects in close relationship to the vertebrate-pathogenic flaviviruses were discovered in mosquitoes. To identify barriers that could block the arboviral vertebrate tropism, we set out to identify the steps at which the ISF replication cycle fails in vertebrates. Our studies revealed blocks at several levels, suggesting that flavivirus host range expansion from insects to vertebrates was a complex process that involved overcoming multiple barriers. PMID:28101536

Stereo-EEG: Diagnostic and therapeutic tool for periventricular nodular heterotopia epilepsies.

PubMed

Mirandola, Laura; Mai, Roberto F; Francione, Stefano; Pelliccia, Veronica; Gozzo, Francesca; Sartori, Ivana; Nobili, Lino; Cardinale, Francesco; Cossu, Massimo; Meletti, Stefano; Tassi, Laura

2017-11-01

Periventricular nodular heterotopias (PNHs) are malformations of cortical development related to neuronal migration disorders, frequently associated with drug-resistant epilepsy (DRE). Stereo-electroencephalography (SEEG) is considered a very effective step of the presurgical evaluation, providing the recognition of the epileptogenic zone (EZ). At the same time, via the intracerebral electrodes it is possible to perform radiofrequency thermocoagulation (SEEG-guided RF-TC) with the aim of ablating and/or disrupting the EZ. The purpose of this study was to evaluate both the relationships between PNH and the EZ, and the efficacy of SEEG-guided RF-TC. Twenty patients with DRE related to PNHs were studied. Inclusion criteria were the following: (1) patients with epilepsy and PNHs (unilateral or bilateral, single or multiple nodules) diagnosed on brain magnetic resonance imaging (MRI); (2) SEEG recordings available as part of the presurgical investigations, with at least one intracerebral electrode inside the heterotopia; (3) complete surgical workup with SEEG-guided RF-TC and/or with traditional neurosurgery, with a follow-up of at least 12 months. Complex and heterogenic epileptic networks were found in these patients. SEEG-guided RF-TC both into the nodules and/or the cortex was efficacious in the 76% of patients. Single or multiple, unilateral or bilateral PNHs are the most suitable for this procedure, whereas patients with PNHs associated with complex cortical malformations obtained excellent outcome only with traditional resective surgery. Each patient had a specific epileptogenic network, independent from the number, size, or location of nodules and from the cortical malformation associated with. SEEG-guided RF-TC appears as a new and very effective diagnostic and therapeutic approach for DRE related to PNHs. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Identification of the TFII-I family target genes in the vertebrate genome.

PubMed

Chimge, Nyam-Osor; Makeyev, Aleksandr V; Ruddle, Frank H; Bayarsaihan, Dashzeveg

2008-07-01

GTF2I and GTF2IRD1 encode members of the TFII-I transcription factor family and are prime candidates in the Williams syndrome, a complex neurodevelopmental disorder. Our previous expression microarray studies implicated TFII-I proteins in the regulation of a number of genes critical in various aspects of cell physiology. Here, we combined bioinformatics and microarray results to identify TFII-I downstream targets in the vertebrate genome. These results were validated by chromatin immunoprecipitation and siRNA analysis. The collected evidence revealed the complexity of TFII-I-mediated processes that involve distinct regulatory networks. Altogether, these results lead to a better understanding of specific molecular events, some of which may be responsible for the Williams syndrome phenotype.

[Lymphatic malformations in the head and neck area].

PubMed

Wiegand, S; Werner, J A

2016-02-01

Lymphatic malformations are congenital malformations of the lymphatic system. They are mainly located in the head and neck area, and grow proportional to the patients' body growth. Depending on the morphology, it can be distinguished between macrocystic, microcystic and mixed lymphatic malformations. Due to their infiltrative growth, microcystic lymphatic malformations are particularly difficult to treat. Therapeutic approaches include conventional surgical resection, laser therapy, sclerotherapy and systemic drug therapies.

Recurrent Hyperammonemia After Abernethy Malformation Type 2 Closure: a Case Report.

PubMed

Li, Hui; Ma, Zhi; Xie, Ying; Tian, Feng

The Abernethy malformation is a rare congenital malformation defined by the presence of an extrahepatic portosystemic shunt. Although most patients are asymptomatic, clinical encephalopathy is present in 15% of cases. We present a patient with type 2 Abernethy malformation, hyperammonemia, and encephalopathy. Shunt closure was performed successfully using interventional angiography; however, hyperammonemia recurred 3 months later. The diagnosis of Abernethy malformation can be made easily, but the ideal patient management strategy has not yet been established. This is the first reported patient with recurrence of hyperammonemia after interventional treatment; we discuss the therapeutic options for Abernethy malformation.

Trematode infection causes malformations and population effects in a declining New Zealand fish.

PubMed

Kelly, David W; Thomas, Harriet; Thieltges, David W; Poulin, Robert; Tompkins, Daniel M

2010-03-01

1. Animal malformations engender wide public and scientific concern because of associated environmental health risks. This is highlighted by increased incidence of limb malformations in amphibians associated with trematode infections and disturbance. Malformations may signal new emerging disease threats, but whether the phenomenon is broadly applicable across taxa, or has population-scale impacts, is unknown. 2. Malformations are widely reported in fish and, until now, have been attributed mainly to contaminants. We tested whether the trematode Telogaster opisthorchis caused severe malformations, leading to population effects, in Galaxias anomalus, a threatened New Zealand freshwater fish. 3. Experimental infection of larval fish caused increasing spinal malformation and mortality with infection intensity that closely matched field patterns. Field malformation frequency peaked in January (65%), before declining sharply in February (25%) and remaining low thereafter. 4. The peak occurred during a 'critical window' of larval development, with the decline coincident with a population crash, indicating that malformation was causing mortality in the field. 5. The occurrence of such critical developmental windows may explain why this mechanism of population impact has been overlooked. With global environmental stressors predicted to enhance trematode infections, our results show that parasite-induced malformation, and its population-scale impacts, could be more widespread than previously considered.

Amphibian malformations

USGS Publications Warehouse

,

1998-01-01

Frog malformations have been reported from 42 states. The broad geographic distribution of these malformations warrants national attention. Scientists at the USGS National Wildlife Health Center in Madison, Wisconsin are studying this problem in an effort to document its scope and to determine the causes of the observed malformations.

Headache in children with Chiari I malformation.

PubMed

Toldo, Irene; Tangari, Marta; Mardari, Rodica; Perissinotto, Egle; Sartori, Stefano; Gatta, Michela; Calderone, Milena; Battistella, Pier Antonio

2014-05-01

Headache is the most common symptom of Chiari 1 malformation, a condition characterized by the herniation of cerebellar tonsils through the foramen magnum. However, the headache pattern of cases with Chiari 1 malformations is not well defined in the literature, especially in children. The aim of this retrospective chart review was to evaluate the frequency and the characteristics of headache in children with Chiari 1 malformation at initial evaluation and during follow up. Forty-five cases with tonsillar ectopia were selected among 9947 cases under 18 years of age who underwent neuroimaging between 2002 and 2010. A semistructured clinical interview (mean follow-up: 5.2 years) was conducted. Headache was classified according to the second edition of the International Classification of Headache Disorders. Possible associations between clinical picture, in particular headache pattern, but also other signs and symptoms attributable to Chiari 1 malformation, and the extent of tonsillar ectopia were found for 3 different groups: those with borderline (<5 mm, N = 12), mild (5-9 mm, N = 27), and severe tonsillar ectopia (≥10 mm, N = 6), respectively. Twenty-four out of 33 (73%) cases with Chiari 1 malformation complained of headache, and 9/33 (27%) of those patients (5 with mild and 4 with severe tonsillar ectopia) reported headache attributed to Chiari 1 malformation. In our studied pediatric population, the most common symptom for cases diagnosed with Chiari 1 malformation was headache, and headache attributed to Chiari 1 malformation was the most common headache pattern in patients with Chiari 1 malformation. The presence of headache attributed to Chiari 1 malformation along with 3 other signs or symptoms of Chiari 1 malformation were highly predictive of severe tonsillar ectopia. © 2014 American Headache Society.

Onyx embolization using dual-lumen balloon catheter: initial experience and technical note.

PubMed

Paramasivam, Srinivasan; Niimi, Yasunari; Fifi, Johanna; Berenstein, Alejandro

2013-10-01

Onyx as an embolization agent for the management of vascular malformation is well established. We report our initial experience with dimethyl-sulphoxide (DMSO) compatible double lumen balloon catheters used for Onyx embolization. Between December 2011 and March 2013, we treated 22 patients aged between 1.5 to 70years with two types of DMSO compatible dual-lumen balloon catheters (Scepter C and Ascent) to treat dural arteriovenous fistulas, brain arteriovenous malformation (AVM) with dural feeders, mandibular, facial, lingual, vertebral and paravertebral AVMs. The catheter has good navigability, compliant balloon on inflation formed a "plug" that has more resistance than Onyx plug enhancing better penetration. During injection, the balloon remained stable without spontaneous deflation or rupture and withstood the pressure build-up well. The retrieval of the catheter in most cases took less than a minute (19/28) while in five, it was less than five minutes and in the remaining four, it was longer that includes a trapped catheter on prolonged attempted retrieval resulted in an epidural hematoma, requiring emergent surgical evacuation. The fluoroscopy time is reduced, as we do not form a proximal onyx plug, the injection time is shorter along with easy and instantaneous removal of the catheter after balloon deflation in most cases. Dual-lumen balloon catheter Onyx embolization is a safe and effective technique. Currently, an important tool to circumvent some of the shortcomings associated with Onyx embolization. The catheter has good navigability, the balloon has stability, tolerance, enhances penetrability. It is easy to retrieve the microcatheter. With the experience gained, and with more compliant balloon catheters available, this technique can be applied to cerebral vessels in near future. Copyright © 2013. Published by Elsevier Masson SAS.

Detachable-Tip Microcatheters for Liquid Embolization of Brain Arteriovenous Malformations and Fistulas: A United States Single-Center Experience.

PubMed

Herial, Nabeel A; Khan, Asif A; Sherr, Gregory T; Qureshi, Mushtaq H; Suri, M Fareed K; Qureshi, Adnan I

2015-09-01

The US Food and Drug Administration recently approved a detachable-tip microcatheter, the Apollo microcatheter (eV3, Inc, Irvine, California), to prevent catheter entrapment during embolization of brain arteriovenous malformations (AVMs) using liquid embolic systems. To report technical aspects and clinical results of cerebral embolizations with the Apollo microcatheter in 7 embolizations in 3 adult patients. A 62-year-old man presented with an AVM in the parieto-occipital region measuring 3.6 × 1.6 cm with major cortical feeders from the right middle cerebral artery (MCA) and minor contribution from the distal right anterior cerebral artery. Two pedicles originating from the MCA were embolized. A 48-year-old woman presented with a left frontal AVM measuring 3.3 × 1.8 cm with arterial feeders from the left MCA, left middle meningeal artery, and contralateral anterior cerebral artery. Three pedicles originating from the left MCA were embolized. A 76-year-old man presented with an arteriovenous fistula with multiple fistulous connections and feeders from both vertebral and occipital arteries and the left posterior cerebral artery draining into the left transverse, torcula, and left sigmoid sinus. Two major occipital artery feeders were embolized. Seven Apollo microcatheters were used with the Onyx 18 liquid embolic system. The length of the detachable tip was 15 mm in 2 and 30 mm in 5 embolizations. The mean microcatheter in-position time within the pedicle was 20 minutes. Detachment of tip occurred in 3 instances. No limitations in accessing target arterial feeders and safe tip disengagement were noted despite prolonged injection times. Our initial experience supports the feasibility, safety, and effectiveness of detachable-tip microcatheters in treating brain AVMs and arteriovenous fistulas.

Biomechanics of metastatic disease in the vertebral column.

PubMed

Whyne, Cari M

2014-06-01

Metastatic disease in the vertebral column compromises the structural stability of the spine leading to increased risk of fracture. The complex patterns of osteolytic and osteoblastic disease within the bony spine have motivated a multimodal approach to better characterize the biomechanics of tumor-involved bone. This review presents our current understanding of the biomechanical behavior of metastatically involved vertebrae, and experimental and computational image-based approaches that have been employed to quantify structural integrity in preclinical models with translation to clinical data sets.

Computer Simulation of Embryonic Systems: What can a virtual embryo teach us about developmental toxicity? Microcephaly: Computational and organotypic modeling of a complex human birth defect (seminar and lecture - Thomas Jefferson University, Philadelphia, PA)

EPA Science Inventory

(1) Standard practice for assessing developmental toxicity is the observation of apical endpoints (intrauterine death, fetal growth retardation, structural malformations) in pregnant rats/rabbits following exposure during organogenesis. EPA’s computational toxicology research pro...

Contemporary occurrence of hydrocephalus and Chiari I malformation in sagittal craniosynostosis. Case report and review of the literature.

PubMed

Sgulò, Francesco Giovanni; Spennato, Pietro; Aliberti, Ferdinando; Di Martino, Giuliana; Cascone, Daniele; Cinalli, Giuseppe

2017-01-01

Chiari malformation type I (CM-I) and hydrocephalus are often associated with complex craniosynostosis. On the contrary, their simultaneous occurrence in monosutural synostosis is extremely rare. The pathophysiological hypothesis is that they may alter posterior fossa growth and lead to cerebellar tonsil herniation also without skull base primary involvement. Hydrocephalus is multifactorial and may be secondary to fourth ventricle outlet obstruction. The management of these cases is quite complex and not well defined. Cranial vault remodeling should be the only treatment when CM-I is asymptomatic and not related to syringomyelia. Suboccipital decompression should be reserved only in complicated CM-I, usually as a second surgical step following the correction of the supratentorial deformity. In our opinion, the associated hydrocephalus should be treated first in order to normalize intracranial hypertension before opening the cranial sutures. We report the case of a 26-month-old child that presented with sagittal craniosynostosis, hydrocephalus, and CM-I. He was managed by performing endoscopic third ventriculostomy (ETV) first and cranial vault remodeling thereafter. Clinico-radiological outcome was very satisfying. Concerning literature is reviewed; physiopathology and surgical management are discussed.

[Development and application of artificial vertebral body].

PubMed

Liu, Jian-Tao; Zhang, Feng; Gao, Zheng-Chao; Niu, Bin-Bin; Li, Yu-Huan; He, Xi-Jing

2017-12-25

Artificial vertebral body has achieved good results in treating spinal tumors, tuberculosis, fracture and other diseases. Currently, artificial vertebral body with variety of kinds and pros and cons, is generally divided into two types: fusion type and movable type. The former according to whether the height could be adjusted and strength of self-stability is divided into three types: support-fixed type, adjust-fixed type and self-fixed type. Whether the height of self-fixed type could be adjusted is dependent on structure of collar thread rotation. The latter is due to mobile device of ball-and-socket joints or hollow structures instead of the disc which retains the activity of the spine to some extent. Materials of artificial vertebral body include metals, ceramics, biomaterials, polymer composites and other materials. Titanium with a dominant role in the metal has developed to the third generation, but there are still defects such as poor surface bioactivity; ceramics with the representative of hydroxyapatite composite, magnetic bioceramics, polycrystalline alumina ceramics and so on, which have the defects of processing complex and uneven mechanical properties; biological material is mainly dominated by xenogeneic bone, which is closest to human bone in structure and properties, but has defects of low toughness and complex production; polymer composites according to biological characteristics in general consists of biodegradable type and non-biodegradable type which are respectively represented by poly-lactide and polyethylene, each with advantages and disadvantages. Although the design and materials of prosthesis have made great progress, it is difficult to fully meet requirements of spinal implants and they need be further optimized. 3D printing technology makes process of the complex structure of prosthesis and individual customization possible and has broad development prospects. However, long production cycles and high cost of defect should be overcome. Although artificial vertebral body has achieved curative effect in treating spinal disease, there were reports of implant loosening or displacement. Combining with evaluation standards not unified, short follow-up time, its exact effect needs further observation. Copyright© 2017 by the China Journal of Orthopaedics and Traumatology Press.

Field surveys of Midwestern and Northeastern Fish and Wildlife Service lands for the presence of abnormal frogs and toads

USGS Publications Warehouse

Converse, K.A.; Mattsson, J.; Eaton-Poole, L.

2000-01-01

The national distribution of information on the discovery of malformations in Minnesota frogs in 1995 stimulated collection and examination of newly metamorphosed frogs during 1996. By late summer and early fall of 1996, malformed frogs and toads were reported on U.S. Fish and Wildlife Service (USFWS) lands in Vermont (Northeast, Region 5) and Minnesota (Midwest, Region 3). In response to these reports, biologists in USFWS Regions 3 and 5 conducted a survey, during the summer of 1997 to determine the distribution and type of malformations in frogs and toads on selected federal lands. Region 3 personnel surveyed 38 field stations at National Wildlife Refuges (NWR's) and Wetland Management Districts. Malformed frogs and toads were collected at 23 (61%) of the Region 3 sites. External malformations were detected in 110 of 6632 individuals representing seven of 13 frog species and one of three toad species examined for an overall of 1.7% affected (percentages for affected species ranged from 0.4-5.2%). In Region 5, 17 NWR's and one National Park were surveyed. Malformed frogs were collected at 10 (56%) of the Region 5 sites. External malformations were detected in 58 of 2267 individuals representing six of 11 frog species and one of two toad species examined for an overall total of 2.6% affected (percentages for affected species ranged from 1.8-15.6%). The majority of malformations observed in frogs and toads collected in Regions 3 and 5 were partially or completely missing hind limbs and digits (50%)or malformed hind limbs and digits (14%). A few individuals had an extra limb or toe, missing or malformed front limb, missing eye, or malformation of the mandible. Despite small sample sizes at some sites, malformations were confirmed to be present in eight species of frogs and two species of toads on Federal lands in USFWS Regions 3 and 5. Further study is needed to determine the extent and distribution of amphibian malformations in these Regions. Data from this study were provided to the national database on distribution of malformed amphibians.

Trace Fossil Evidence of Trematode-Bivalve Parasite-Host Interactions in Deep Time.

PubMed

Huntley, John Warren; De Baets, Kenneth

2015-01-01

Parasitism is one of the most pervasive phenomena amongst modern eukaryotic life and yet, relative to other biotic interactions, almost nothing is known about its history in deep time. Digenean trematodes (Platyhelminthes) are complex life cycle parasites, which have practically no body fossil record, but induce the growth of characteristic malformations in the shells of their bivalve hosts. These malformations are readily preserved in the fossil record, but, until recently, have largely been overlooked by students of the fossil record. In this review, we present the various malformations induced by trematodes in bivalves, evaluate their distribution through deep time in the phylogenetic and ecological contexts of their bivalve hosts and explore how various taphonomic processes have likely biased our understanding of trematodes in deep time. Trematodes are known to negatively affect their bivalve hosts in a number of ways including castration, modifying growth rates, causing immobilization and, in some cases, altering host behaviour making the host more susceptible to their own predators. Digeneans are expected to be significant agents of natural selection. To that end, we discuss how bivalves may have adapted to their parasites via heterochrony and suggest a practical methodology for testing such hypotheses in deep time. Copyright © 2015 Elsevier Ltd. All rights reserved.

Atretic cephalocele: the tip of the iceberg.

PubMed

Martinez-Lage, J F; Sola, J; Casas, C; Poza, M; Almagro, M J; Girona, D G

1992-08-01

Atretic cephalocele appears as an unimportant and benign lesion. This malformation consists of meningeal and vestigial tissues (arachnoid, glial, or central nervous system rests). The authors report the findings in 16 cases (seven parietal and nine occipital) of rudimentary cephaloceles. Twelve patients presented with associated brain abnormalities detected by either computerized tomography (CT) or magnetic resonance imaging (MR). Nine lesions also exhibited an anomalous vascular component demonstrated by CT or MR imaging or at surgery. The existence of this tiny malformation in five cases was the main diagnostic clue to a severe complex of cerebral anomalies, namely cerebro-oculomuscular (Walker-Warburg) syndrome. An occipital location of the atretic cephalocele was associated with the worst prognosis, with only two children developing normally. However, a parietal location carried a better prognosis, which is contrary to the outcome reported in the current literature. The authors classify atretic cephaloceles into two types based on histological examination of the surgical specimens, and suggest that these types represent different stages in the development of this malformation. It is concluded that, in the evaluation of the atretic cephalocele, the neurosurgeon is obliged to proceed to a detailed neuroradiological study of the patient and that the prognosis does not depend on the existence of the cephalocele itself, but rather on associated "occult" brain anomalies.

A case of pancreatic AV malformation in an elderly man.

PubMed

Gupta, Vipin; Kedia, Saurabh; Sonika, Ujjwal; Madhusudhan, Kumble Seetharama; Pal, Sujoy; Garg, Pramod

2018-06-01

A 60-year-old man presented with recurrent abdominal pain and weight loss for 6 months. Abdominal imaging showed a large vascular lesion in the head and neck of pancreas suggestive of arteriovenous malformation (AV malformation). Endoscopic ultrasound was done which showed features of AV malformation with no evidence of pancreatic malignancy. Surgery was planned for definitive treatment of malformation. Digital subtraction angiography with angioembolization was done prior to surgery to reduce vascularity of the lesion. He recovered after a pylorus preserving pancreaticoduodenectomy. Histopathology of the resected specimen confirmed the pancreatic AV malformation. There has been no recurrence at 2 years of follow-up.

Identification of vimentin- and elastin-like transcripts specifically expressed in developing notochord of Atlantic salmon (Salmo salar L.).

PubMed

Sagstad, Anita; Grotmol, Sindre; Kryvi, Harald; Krossøy, Christel; Totland, Geir K; Malde, Ketil; Wang, Shou; Hansen, Tom; Wargelius, Anna

2011-11-01

The notochord functions as the midline structural element of all vertebrate embryos, and allows movement and growth at early developmental stages. Moreover, during embryonic development, notochord cells produce secreted factors that provide positional and fate information to a broad variety of cells within adjacent tissues, for instance those of the vertebrae, central nervous system and somites. Due to the large size of the embryo, the salmon notochord is useful to study as a model for exploring notochord development. To investigate factors that might be involved in notochord development, a normalized cDNA library was constructed from a mix of notochords from ∼500 to ∼800 day°. From the 1968 Sanger-sequenced transcripts, 22 genes were identified to be predominantly expressed in the notochord compared to other organs of salmon. Twelve of these genes were found to show expressional regulation around mineralization of the notochord sheath; 11 genes were up-regulated and one gene was down-regulated. Two genes were found to be specifically expressed in the notochord; these genes showed similarity to vimentin (acc. no GT297094) and elastin (acc. no GT297478). In-situ results showed that the vimentin- like transcript was expressed in both chordocytes and chordoblasts, whereas the elastin- like transcript was uniquely expressed in the chordoblasts lining the notochordal sheath. In salmon aquaculture, vertebral deformities are a common problem, and some malformations have been linked to the notochord. The expression of identified transcripts provides further insight into processes taking place in the developing notochord, prior to and during the early mineralization period.

Experimental Crossing of Two Distinct Species of Leopard Geckos, Eublepharis angramainyu and E. macularius: Viability, Fertility and Phenotypic Variation of the Hybrids

PubMed Central

Jančúchová-Lásková, Jitka; Landová, Eva; Frynta, Daniel

2015-01-01

Hybridization between distinct species of animals and subsequent genetic introgression plays a considerable role in the speciation process and the emergence of adaptive characters. Fitness of between-species hybrids usually sharply decreases with the divergence time of the concerned species and the divergence depth, which still allows for a successful crossing differs among principal clades of vertebrates. Recently, a review of hybridization events among distinct lizard species revealed that lizards belong to vertebrates with a highly developed ability to hybridize. In spite of this, reliable reports of experimental hybridizations between genetically fairly divergent species are only exceptional. Here, we show the results of the crossing of two distinct allopatric species of eyelid geckos possessing temperature sex determination and lacking sex chromosomes: Eublepharis macularius distributed in Pakistan/Afghanistan area and E. angramainyu, which inhabits Mesopotamia and adjacent areas. We demonstrated that F1 hybrids were viable and fertile, and the introgression of E. angramainyu genes into the E. macularius genome can be enabled via a backcrossing. The examined hybrids (except those of the F2 generation) displayed neither malformations nor a reduced survival. Analyses of morphometric and coloration traits confirmed phenotypic distinctness of both parental species and their F1 hybrids. These findings contrast with long-term geographic and an evolutionary separation of the studied species. Thus, the occurrence of fertile hybrids of comparably divergent species, such as E. angramainyu and E. macularius, may also be expected in other taxa of squamates. This would violate the current estimates of species diversity in lizards. PMID:26633648

Amphibian malformations and body condition across an agricultural landscape of northwest Argentina.

PubMed

Guerra, Cecilia; Aráoz, Ezequiel

2016-09-26

Agricultural landscapes support large amphibian populations because they provide habitat for many species, although agriculture affects amphibians through various mechanisms. Pollution with agrochemicals is the major threat to amphibian populations after habitat loss, as chemicals alter the ecophysiology of amphibians, putting their health and survival at risk. We aimed to assess the effect of different environments, sites, width of forest buffers and sampling years on the health of amphibians, which was estimated through the prevalence of malformations and body condition. During 3 yr of pitfall trapping, we captured 4491 amphibians. The prevalence of malformations was higher in the croplands than in the forests, while the body condition was better within forests. The prevalence of malformations was higher in the narrower forest site than in the wider forest site. The prevalence of malformations and the body condition were higher in the third year. The prevalence of malformations differed by species. We found 11 types of malformation, which mainly affected limbs and were unilateral or bilaterally asymmetrical. Our results showed that the prevalence of malformations and body condition reflect different aspects of the health of amphibians and that forest individuals are healthier than those from croplands. The results also highlight the importance of spatial configuration besides the conservation of natural habitats to preserve healthy amphibians in agricultural landscapes. The types of malformation that we found suggest that agrochemicals could be an important cause of malformations.

Associated malformations among infants with anophthalmia and microphthalmia.

PubMed

Stoll, Claude; Dott, Beatrice; Alembik, Yves; Roth, Marie-Paule

2012-03-01

Infants with anophthalmia and microphthalmia frequently have other associated congenital anomalies. The reported frequency and types of associated malformations vary among different studies. The purpose of this investigation was to assess the frequency and types of associated malformations among infants with anophthalmia and microphthalmia in a geographically well defined population from 1979 to 2004 of 346,831 consecutive births. Of the 87 infants with anophthalmia and microphthalmia born during this period (prevalence at birth, 2.5 per 10,000), 90% had associated malformations. Infants with associated malformation were divided into recognizable conditions (22 infants [25%] with chromosomal and 15 infants [17%] with nonchromosomal conditions), and nonrecognizable conditions (41 infants [47%] with multiple malformations). Trisomies 13 and 18 were the most frequent chromosomal abnormalities. Amniotic bands sequence, CHARGE syndrome, Meckel-Gruber syndrome, and VACTERL association were most often present in recognizable nonchromosomal conditions. Malformations in the musculoskeletal, cardiovascular, and central nervous systems were the most common other anomalies in infants with multiple malformations and nonrecognizable conditions. The frequency of associated malformations in infants with anophthalmia or microphthalmia emphasizes the need for a thorough investigation of these infants. Routine screening for other malformations-especially musculoskeletal, cardiac, and central nervous system anomalies-may need to be considered in infants with anophthalmia or microphthalmia, and referral of these infants for genetics evaluation and counseling seems warranted. Copyright © 2012 Wiley Periodicals, Inc.

Progesterone receptors identified in vascular malformations of the head and neck.

PubMed

Duyka, Landon J; Fan, Chun Y; Coviello-Malle, Jean M; Buckmiller, Lisa; Suen, James Y

2009-10-01

To identify hormone receptors within vascular malformations (arteriovenous malformations [AVMs], venous malformations [VMs], and lymphatic malformations [LMs]) of the head and neck. Immunohistochemical staining for estrogen receptor (ER) and progesterone receptor (PR) was performed on archival vascular malformation tissue collected from both pediatric and adult patients. Tertiary referral center from 2006 to 2008. Twelve AVM, 10 VM, and eight LM specimens were stained for both ER and PR. Ten breast carcinoma specimens were used as controls, with the carcinoma cells serving as positive controls, and the endothelium and smooth muscle cells of the blood vessels serving as negative controls. Five normal supraglottic mucosal samples served as head and neck controls. The Fisher exact test was used for statistical analysis. Ten of the 12 (83%) AVM specimens stained diffusely positive for PR within the nuclei of the endothelium and smooth muscle of the malformed vessels (P < 0.0001). Five of the 10 (50%) VM specimens stained positive for PR (2 [20%] focal, 3 [30%] diffuse) within the nuclei of the endothelium and smooth muscle of the malformed vessels (P = 0.0325). Four of the eight (50%) LM specimens stained focally positive for PR within the nuclei of the endothelium of the malformed vessels (P = 0.0229). None of the vascular malformation specimens stained positive for ER. Our data suggest that PR, but not ER, is expressed in AVMs, VMs, and LMs of the head and neck.

The Immunoglobulins of Cold-Blooded Vertebrates

PubMed Central

Pettinello, Rita; Dooley, Helen

2014-01-01

Although lymphocyte-like cells secreting somatically-recombining receptors have been identified in the jawless fishes (hagfish and lamprey), the cartilaginous fishes (sharks, skates, rays and chimaera) are the most phylogenetically distant group relative to mammals in which bona fide immunoglobulins (Igs) have been found. Studies of the antibodies and humoral immune responses of cartilaginous fishes and other cold-blooded vertebrates (bony fishes, amphibians and reptiles) are not only revealing information about the emergence and roles of the different Ig heavy and light chain isotypes, but also the evolution of specialised adaptive features such as isotype switching, somatic hypermutation and affinity maturation. It is becoming increasingly apparent that while the adaptive immune response in these vertebrate lineages arose a long time ago, it is most definitely not primitive and has evolved to become complex and sophisticated. This review will summarise what is currently known about the immunoglobulins of cold-blooded vertebrates and highlight the differences, and commonalities, between these and more “conventional” mammalian species. PMID:25427250

Two Rounds of Whole Genome Duplication in the Ancestral Vertebrate

PubMed Central

Dehal, Paramvir; Boore, Jeffrey L

2005-01-01

The hypothesis that the relatively large and complex vertebrate genome was created by two ancient, whole genome duplications has been hotly debated, but remains unresolved. We reconstructed the evolutionary relationships of all gene families from the complete gene sets of a tunicate, fish, mouse, and human, and then determined when each gene duplicated relative to the evolutionary tree of the organisms. We confirmed the results of earlier studies that there remains little signal of these events in numbers of duplicated genes, gene tree topology, or the number of genes per multigene family. However, when we plotted the genomic map positions of only the subset of paralogous genes that were duplicated prior to the fish–tetrapod split, their global physical organization provides unmistakable evidence of two distinct genome duplication events early in vertebrate evolution indicated by clear patterns of four-way paralogous regions covering a large part of the human genome. Our results highlight the potential for these large-scale genomic events to have driven the evolutionary success of the vertebrate lineage. PMID:16128622

Familial Aggregation of Chiari Malformation: Presentation, Pedigree, and Review of the Literature.

PubMed

Nagy, Laszlo; Mobley, James; Ray, Coby

2016-01-01

This article reports the largest familial aggregation of Chiari malformation in a single family to date as reported in the literature. This study is a retrospective case series of a family of whom five individuals have a confirmed case of Chiari malformation and three additional individuals have Chiari signs and symptoms. This contribution further supports the implication of genetics in the transmission of Chiari malformation. The family reported in this study also has a significant incidence of Ehlers-Danlos. Three sisters, including a set of twins, presented with confirmed cases of Chiari malformation and four of the five children of the twin sisters presented with confirmed or suspected Chiari malformation. Of note, the non-twin sister has three children who are unaffected. This report provides further evidence for a shared loci between the Chiari malformation and Ehlers-Danlos.

Head and neck vascular malformations: time-resolved MR projection angiography.

PubMed

Ziyeh, S; Schumacher, M; Strecker, R; Rössler, J; Hochmuth, A; Klisch, J

2003-10-01

Extracranial vascular anomalies can be divided into haemangiomas and vascular malformations. The latter can be subdivided on the basis of the predominant type of vascular channels. Separation of high- and low-flow vascular malformations is of clinical importance. We report preliminary observations on time-resolved magnetic resonance projection angiography (MRPA) of vascular malformations of the head and neck. We examined eight patients with vascular anomalies of the head and neck. On MRPA the time between the early arterial phase and enhancement of the malformation could be used to distinguish high- and low-flow lesions. High-flow arteriovenous malformations showed early, intense enhancement. Venous malformations were either not visible on MRPA or showed late enhancement of veins. One patient was examined after embolisation of an arteriovenous fistula of the mandible. Normal MRPA was taken to indicate absence of a residual lesion.

Early evolution of multifocal optics for well-focused colour vision in vertebrates.

PubMed

Gustafsson, O S E; Collin, S P; Kröger, R H H

2008-05-01

Jawless fishes (Agnatha; lampreys and hagfishes) most closely resemble the earliest stage in vertebrate evolution and lamprey-like animals already existed in the Lower Cambrian [about 540 million years ago (MYA)]. Agnathans are thought to have separated from the main vertebrate lineage at least 500 MYA. Hagfishes have primitive eyes, but the eyes of adult lampreys are well-developed. The southern hemisphere lamprey, Geotria australis, possesses five types of opsin genes, three of which are clearly orthologous to the opsin genes of jawed vertebrates. This suggests that the last common ancestor of all vertebrate lineages possessed a complex colour vision system. In the eyes of many bony fishes and tetrapods, well-focused colour images are created by multifocal crystalline lenses that compensate for longitudinal chromatic aberration. To trace the evolutionary origins of multifocal lenses, we studied the optical properties of the lenses in four species of lamprey (Geotria australis, Mordacia praecox, Lampetra fluviatilis and Petromyzon marinus), with representatives from all three of the extant lamprey families. Multifocal lenses are present in all lampreys studied. This suggests that the ability to create well-focused colour images with multifocal optical systems also evolved very early.

CRISPR/Cas9-mediated mutagenesis in the sea lamprey Petromyzon marinus: a powerful tool for understanding ancestral gene functions in vertebrates

PubMed Central

Square, Tyler; Romášek, Marek; Jandzik, David; Cattell, Maria V.; Klymkowsky, Michael; Medeiros, Daniel M.

2015-01-01

Lamprey is one of only two living jawless vertebrates, a group that includes the first vertebrates. Comparisons between lamprey and jawed vertebrates have yielded important insights into the origin and evolution of vertebrate physiology, morphology and development. Despite its key phylogenetic position, studies of lamprey have been limited by their complex life history, which makes traditional genetic approaches impossible. The CRISPR/Cas9 system is a bacterial defense mechanism that was recently adapted to achieve high-efficiency targeted mutagenesis in eukaryotes. Here we report CRISPR/Cas9-mediated disruption of the genes Tyrosinase and FGF8/17/18 in the sea lamprey Petromyzon marinus, and detail optimized parameters for producing mutant F0 embryos. Using phenotype and genotype analyses, we show that CRISPR/Cas9 is highly effective in the sea lamprey, with a majority of injected embryos developing into complete or partial mutants. The ability to create large numbers of mutant embryos without inbred lines opens exciting new possibilities for studying development in lamprey and other non-traditional model organisms with life histories that prohibit the generation of mutant lines. PMID:26511928

Diagnostic imaging of solitary tumors of the spine: what to do and say.

PubMed

Rodallec, Mathieu H; Feydy, Antoine; Larousserie, Frédérique; Anract, Philippe; Campagna, Raphaël; Babinet, Antoine; Zins, Marc; Drapé, Jean-Luc

2008-01-01

Metastatic disease, myeloma, and lymphoma are the most common malignant spinal tumors. Hemangioma is the most common benign tumor of the spine. Other primary osseous lesions of the spine are more unusual but may exhibit characteristic imaging features that can help the radiologist develop a differential diagnosis. Radiologic evaluation of a patient who presents with osseous vertebral lesions often includes radiography, computed tomography (CT), and magnetic resonance (MR) imaging. Because of the complex anatomy of the vertebrae, CT is more useful than conventional radiography for evaluating lesion location and analyzing bone destruction and condensation. The diagnosis of spinal tumors is based on patient age, topographic features of the tumor, and lesion pattern as seen at CT and MR imaging. A systematic approach is useful for recognizing tumors of the spine with characteristic features such as bone island, osteoid osteoma, osteochondroma, chondrosarcoma, vertebral angioma, and aneurysmal bone cyst. In the remaining cases, the differential diagnosis may include other primary spinal tumors, vertebral metastases and major nontumoral lesions simulating a vertebral tumor, Paget disease, spondylitis, echinococcal infection, and aseptic osteitis. In many cases, vertebral biopsy is warranted to guide treatment.

Drosophila contactin, a homolog of vertebrate contactin, is required for septate junction organization and paracellular barrier function.

PubMed

Faivre-Sarrailh, Catherine; Banerjee, Swati; Li, Jingjun; Hortsch, Michael; Laval, Monique; Bhat, Manzoor A

2004-10-01

Septate junctions (SJs) in epithelial and neuronal cells play an important role in the formation and maintenance of charge and size selective barriers. They form the basis for the ensheathment of nerve fibers in Drosophila and for the attachment of myelin loops to axonal surface in vertebrates. The cell-adhesion molecules NRX IV/Caspr/Paranodin (NCP1), contactin and Neurofascin-155 (NF-155) are all present at the vertebrate axo-glial SJs. Mutational analyses have shown that vertebrate NCP1 and its Drosophila homolog, Neurexin IV (NRX IV) are required for the formation of SJs. In this study, we report the genetic, molecular and biochemical characterization of the Drosophila homolog of vertebrate contactin, CONT. Ultrastructural and dye-exclusion analyses of Cont mutant embryos show that CONT is required for organization of SJs and paracellular barrier function. We show that CONT, Neuroglian (NRG) (Drosophila homolog of NF-155) and NRX IV are interdependent for their SJ localization and these proteins form a tripartite complex. Hence, our data provide evidence that the organization of SJs is dependent on the interactions between these highly conserved cell-adhesion molecules.

The Chiari 3 Malformation and a Systemic Review of the Literature.

PubMed

Young, Richard M; Shafa, Justin S; Myseros, John S

2015-01-01

Chiari type 3 is a rare hindbrain malformation that has been reported in the literature primarily as case reports and case series. Radiological, pathophysiological and surgical definitions of the malformation are inconsistent in the literature and subsequently can be confusing, and outcomes have also been uniformly poor. The definition of this rare malformation will be clarified through a case presentation. A retrospective review of prior publications in the PubMed and MEDLINE databases was performed looking for reports of 'Chiari 3 +/- malformation' and 'occipital encephalocele'. Relevant papers were reviewed and compiled into table format with associated descriptions of a Chiari type 3 malformation. A case illustration is presented with radiological and intraoperative imaging to reinforce and clarify the definition. Upon review of the prior publications in the detail of the descriptions and imaging associated with each article, there is a wide range of variability in the description of what is considered a Chiari 3 malformation. Occipital, occipitocervical and high cervical defects have all been described as Chiari 3 malformation. Our case illustration presents a patient with an occipitocervical encephalocele with neural elements, which is the classic and accepted definition of the Chiari 3 malformation. Chiari type 3 is a rare congenital malformation, and prior publications describing this developmental disorder have not demonstrated a consensus in its definition. In addition, outcomes have traditionally been reported as poor. This case illustration of a Chiari type 3 enforces the definition of an occipitocervical encephalocele with hindbrain herniation, and with proper management not all Chiari 3 malformation patients have bad outcomes. © 2015 S. Karger AG, Basel.

Coblation vertebroplasty for complex vertebral insufficiency fractures.

PubMed

Wilson, David J; Owen, Sara; Corkill, Rufus A

2013-07-01

Coblation to create a cavity in the affected vertebral body was performed for complex fractures and/or when there was a posterior wall defect. This permitted a low-pressure injection and potentially reduces the risk of extravasation of cement into the spinal canal. Prospective audit for outcome measures and complications allowed retrospective review of cases treated by coblation. A commercial wand inserted via a wide-bore vertebroplasty needle created a cavity before inserting cement. A visual analogue scale assessed pain and Roland Morris scoring assessed mobility. Thirty-two coblation procedures were performed. Primary diagnoses were myeloma, metastases, osteoporosis and trauma. Outcome measures were recorded with a 56 % success rate, 6 % no change and 32 % with mixed but mainly positive results; 6 % died before follow-up. No complications were observed; in particular no patient suffered neurological damage and none have developed subsequent fractures at the treated levels. This technique makes possible cementation of patients who would otherwise be unsuitable for vertebroplasty. The modest pain and disability improvement is partly due to our stringent criteria as well as fracture complexity. Further work will assess the efficacy of the method compared with conservative measures. • Treatment of vertebral compression fractures with possible posterior wall defects is controversial. • Coblation before vertebroplasty allows a low-pressure injection into fractured vertebrae. • This technique reduces risk of extravasation of cement. • No serious complication of our coblation procedures was observed.

Notch-1 Signalling Is Activated in Brain Arteriovenous Malformations in Humans

ERIC Educational Resources Information Center

ZhuGe, Qichuan; Zhong, Ming; Zheng, WeiMing; Yang, Guo-Yuan; Mao, XiaoOu; Xie, Lin; Chen, Gourong; Chen, Yongmei; Lawton, Michael T.; Young, William L.; Greenberg, David A.; Jin, Kunlin

2009-01-01

A role for the Notch signalling pathway in the formation of arteriovenous malformations during development has been suggested. However, whether Notch signalling is involved in brain arteriovenous malformations in humans remains unclear. Here, we performed immunohistochemistry on surgically resected brain arteriovenous malformations and found that,…

Prevalence, prenatal diagnosis and clinical features of oculo-auriculo-vertebral spectrum: a registry-based study in Europe

PubMed Central

Barisic, Ingeborg; Odak, Ljubica; Loane, Maria; Garne, Ester; Wellesley, Diana; Calzolari, Elisa; Dolk, Helen; Addor, Marie-Claude; Arriola, Larraitz; Bergman, Jorieke; Bianca, Sebastiano; Doray, Berenice; Khoshnood, Babak; Klungsoyr, Kari; McDonnell, Bob; Pierini, Anna; Rankin, Judith; Rissmann, Anke; Rounding, Catherine; Queisser-Luft, Annette; Scarano, Gioacchino; Tucker, David

2014-01-01

Oculo-auriculo-vertebral spectrum is a complex developmental disorder characterised mainly by anomalies of the ear, hemifacial microsomia, epibulbar dermoids and vertebral anomalies. The aetiology is largely unknown, and the epidemiological data are limited and inconsistent. We present the largest population-based epidemiological study to date, using data provided by the large network of congenital anomalies registries in Europe. The study population included infants diagnosed with oculo-auriculo-vertebral spectrum during the 1990–2009 period from 34 registries active in 16 European countries. Of the 355 infants diagnosed with oculo-auriculo-vertebral spectrum, there were 95.8% (340/355) live born, 0.8% (3/355) fetal deaths, 3.4% (12/355) terminations of pregnancy for fetal anomaly and 1.5% (5/340) neonatal deaths. In 18.9%, there was prenatal detection of anomaly/anomalies associated with oculo-auriculo-vertebral spectrum, 69.7% were diagnosed at birth, 3.9% in the first week of life and 6.1% within 1 year of life. Microtia (88.8%), hemifacial microsomia (49.0%) and ear tags (44.4%) were the most frequent anomalies, followed by atresia/stenosis of external auditory canal (25.1%), diverse vertebral (24.3%) and eye (24.3%) anomalies. There was a high rate (69.5%) of associated anomalies of other organs/systems. The most common were congenital heart defects present in 27.8% of patients. The prevalence of oculo-auriculo-vertebral spectrum, defined as microtia/ear anomalies and at least one major characteristic anomaly, was 3.8 per 100 000 births. Twinning, assisted reproductive techniques and maternal pre-pregnancy diabetes were confirmed as risk factors. The high rate of different associated anomalies points to the need of performing an early ultrasound screening in all infants born with this disorder. PMID:24398798

Whole Genome Duplications Shaped the Receptor Tyrosine Kinase Repertoire of Jawed Vertebrates.

PubMed

Brunet, Frédéric G; Volff, Jean-Nicolas; Schartl, Manfred

2016-06-03

The receptor tyrosine kinase (RTK) gene family, involved primarily in cell growth and differentiation, comprises proteins with a common enzymatic tyrosine kinase intracellular domain adjacent to a transmembrane region. The amino-terminal portion of RTKs is extracellular and made of different domains, the combination of which characterizes each of the 20 RTK subfamilies among mammals. We analyzed a total of 7,376 RTK sequences among 143 vertebrate species to provide here the first comprehensive census of the jawed vertebrate repertoire. We ascertained the 58 genes previously described in the human and mouse genomes and established their phylogenetic relationships. We also identified five additional RTKs amounting to a total of 63 genes in jawed vertebrates. We found that the vertebrate RTK gene family has been shaped by the two successive rounds of whole genome duplications (WGD) called 1R and 2R (1R/2R) that occurred at the base of the vertebrates. In addition, the Vegfr and Ephrin receptor subfamilies were expanded by single gene duplications. In teleost fish, 23 additional RTK genes have been retained after another expansion through the fish-specific third round (3R) of WGD. Several lineage-specific gene losses were observed. For instance, birds have lost three RTKs, and different genes are missing in several fish sublineages. The RTK gene family presents an unusual high gene retention rate from the vertebrate WGDs (58.75% after 1R/2R, 64.4% after 3R), resulting in an expansion that might be correlated with the evolution of complexity of vertebrate cellular communication and intracellular signaling. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Defining Ebstein's malformation using three-dimensional echocardiography.

PubMed

Vettukattil, Joseph J; Bharucha, Tara; Anderson, Robert H

2007-12-01

Ebstein's malformation is difficult to visualise, for both the echocardiographer and the surgeon. The essence of the problem in Ebstein's malformation is the deviation of the hingepoints of the leaflets towards the junctions of the inlet and apical trabecular parts of the right ventricle. Three-dimensional echocardiography offers new insights into the morphology and function of malformed valves, and allows elucidation of all the features. It allows clear visualisation of the valve leaflets, showing the precise morphology of the valve leaflets, the extent of their formation, the level of their attachment, and their degree of coaptation. Visualisation of the mechanism of regurgitation or stenosis is possible, as is more accurate quantification of the regurgitant jet or jets. Subchordal apparatus may be seen more clearly using three-dimensional echocardiography, and their functional anatomy understood. The multiplanar review modality allows examination of the three-dimensional data set even in patients with sub-optimal echocardiographic imaging. Previously, much of this information could only be well-understood at the time of surgery or post mortem, meaning that the majority of the specimens fully examined were at the poorly functioning end of the spectrum. This information is of use in furthering our understanding of this complex lesion as it functions in vivo, and demonstrating which anatomical pathology is significant in producing functional and physiological consequences. It is also of use for the clinician in selecting which patients are amenable to surgical intervention, for either single or biventricular repair, and for the surgeon in planning how to approach the operation. Correlation between three-dimensional echocardiographic findings and surgical findings has already been established, but the effect of this enhanced anatomical knowledge on surgical planning and surgical outcome requires further investigation.

PHACE syndrome: new views on diagnostic criteria.

PubMed

Poetke, M; Frommeld, T; Berlien, H P

2002-12-01

The association of large facial hemangiomas with posterior fossa malformations and vascular anomalies has been termed the PHACE syndrome. It is characterized by the association of posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta and other cardiac defects, and eye abnormalities. Since most articles focus on isolated case reports, an extended retrospective literature review of all reports of large hemangiomas with associated abnormalities of the central nervous system and other malformations was performed to examine the clinical features, and other not as yet reported associated anomalies. Reports were found on 59 patients with PHACE syndrome, to which we added ten cases of our own. The Dandy-Walker syndrome is the most common CNS abnormality reported in association with PHACE syndrome and was seen in 48 (81 %) patients. Arterial malformations were found in 13 (22 %) cases; only 11 patients (19 %) had structural arterial abnormalities without associated Dandy-Walker complex. As published, about one third of patients (31 %) had further ophthalmologic abnormalities, and cardiac anomalies, including coarctation of the aorta. Subglottic hemangiomas were seen in 4 (7 %) patients and ventral developmental defects also in 3 cases. In seven of 59 patients (12 %) with PHACE syndrome, intracranial hemangiomas were present. This study demonstrates that among other CNS abnormalities, special attention should be given to intracranial hemangiomas which seems to be a peculiar phenotype of PHACE syndrome. We therefore suggest that a sixth criterion should be added to the five minimal inclusion criteria for PHACE syndrome. The inclusion criteria would then be: arterial abnormalities or/and intracranial hemangiomas. On the basis of our experience with our patients and with those previously reported, we stress the importance of using contrast-enhanced imaging to detect intracranial lesions.

Craniofacial structure alterations of foetuses from folic acid deficient pregnant mice.

PubMed

Maldonado, Estela; López, Yamila; Herrera, Manuel; Martínez-Sanz, Elena; Martínez-Álvarez, Concepción; Pérez-Miguelsanz, Juliana

2018-03-28

Craniofacial development in mammals is a complex process that involves a coordinated series of molecular and morphogenetic events. Folic acid (FA) deficiency has historically been associated with congenital spinal cord malformations, but the effect that a maternal diet deficient in FA has on the development of other structures has been poorly explored. In the present study, the objective was to describe and quantify the alterations of craniofacial structures presented in mouse foetuses from dams fed a FA deficient (FAD) diet compared with controls that were given a regular maternal diet. E17 mouse foetuses were removed from dams that were fed with a control diet or with a FAD diet for several weeks. Foetuses with maternal FAD diets were selected for the study when they showed an altered tongue or mandible. Histological sections were used to quantify the dimensions of the head, tongue, mandibular bone and masseter muscle areas using ImageJ software. The muscles of the tongue, suprahyoid muscles, lingual septum, submandibular ducts, and lingual arteries were also analysed. The heads of malformed foetuses were smaller than the heads of the controls, and they showed different types of malformations: microglossia with micrognathia (some of which were combined with cleft palate) and aglossia with either micrognathia or agnathia. Lingual and suprahyoid muscles were affected in different forms and degrees. We also found alterations in the lingual arteries and in the ducts of the submandibular glands. Summarised we can state that pharyngeal arches-derived structures were affected, and the main malformations observed corroborate the vulnerability of cranial neural crest cells to FA deficiency. The present study reveals alterations in the development of craniofacial structures in FAD foetuses. This study provides a new focus for the role of FA during embryological development. Copyright © 2018 Elsevier GmbH. All rights reserved.

Medico-legal and ethical problems associated with treatment of children born with congenital malformations.

PubMed

Foo, K B

1994-04-01

Recent advances in medicine and biomedical science have brought in their wake a whole array of moral, ethical and medico-legal problems. For eg, in relation to the withholding or withdrawal of treatment of neonates born with congenital malformations. While the technology to treat and thus to artificially prolong life is available, the related question of whether or not to do so and in what circumstances has to be considered. There is a paucity of cases in the courts. However, some useful principles can be drawn from a number of cases in the UK. The search for clearer legal and moral criteria has become more urgent. A way ahead appears to lie in the formation of Hospital Review Committees or some such mechanism which would enable the most appropriate decision to be taken in any one case bearing in mind the complex ethical and medico-legal issues involved.

Individualized treatment of craniovertebral junction malformation guided by intraoperative computed tomography.

PubMed

Li, Lianfeng; Wang, Peng; Chen, LiFeng; Ma, Xiaodong; Bu, Bo; Yu, Xinguang

2012-04-01

This study was designed to report our preliminary experience of intraoperative computed tomography (iCT) using a mobile scanner with integrated neuronavigation system (NNS). The objective of this study was to assess the feasibility and potential utility of iCT with integrated NNS in individualized treatment of craniovertebral junction malformation (CVJM). The surgical management of congenital craniovertebral anomalies is complex due to the relative difficulty in accessing the region, critical relationships of neurovascular structures, and the intricate biomechanical issues involved. We reported our first 19 complex CVJM cases including 11 male and 8 female patients from January, 2009 to June, 2009 (mean age, 33.9 y; age range, 13 to 58 y). A sliding gantry 40-slice CT scanner was installed in a preexisting operating room. Image data was transferred directly from the scanner into the NNS using an automated registration system. We applied this technology to transoral odontoidectomy in 17 patients. Moreover, with the extra help of iCT integrated with NNS, odontoidectomy through posterior midline approach, and transoral atlantal lateral mass resection were, for the first time, performed for treatment of complex CVJM. NNS was found to correlate well with the intraoperative findings, and the recalibration was uneven in all cases with an accuracy of 1.6 mm (1.6: 1.2 to 2.0). All patients were clinically evaluated by Nurick grade criteria, and neurological deficits were monitored after 3 months of surgery. Fifteen patients (79%) were improved by at least 1 Nurick grade, whereas the grade did not change in 4 patients (21%). iCT scanning with integrated NNS was both feasible and beneficial for the surgical management of complex CVJM. In this unusual patient population, the technique seemed to be valuable in negotiating complex anatomy and achieving a safe and predictable decompression.

[Polythelia and renal malformation].

PubMed

Jójárt, G; Seres, E

1992-07-12

The authors found 241 polythelia (5.86) among 4113 schoolchildren (aged 6-14 years). They investigated 236 of the 241 with ultrasound and found 10 renal malformations (4.24%). Among 280 controls with respiratory infection, accident or tonsillectomy they found 9 renal malformations (3.21%). With screening of 1635 neonates they found 66 with accessory nipples (4.05%). Two of the 66 had renal malformations (3.03%), while among the 1957 control neonates 37 had renal malformations (1.89%). In the hospital and ambulancy the authors found 106 polythelia, five of them had renal abnormalities (4.72%). The authors did not found association of polythelia and renal malformation with ultrasound investigation of 408 children with polythelia.

Development of profound Chiari I malformation and cerebellar tissue loss and resolution following shunting of posterior fossa extra-axial cyst. Case report.

PubMed

Khan, Rabia; Oakes, Peter; Tubbs, R Shane; Oakes, W Jerry

2017-01-01

Chiari I malformation can be due to a multitude of etiologies such as craniosynostosis or hydrocephalus. A posterior fossa extra-axial cyst (PFEAC) appears to be an extremely rare cause of this form of hindbrain herniation. Herein, we report a case of PFEAC that presented with no Chiari I malformation and then presented months later with a significant Chiari I malformation. Following shunt placement of a PFEAC, striking reversal of the Chiari malformation as well as reconstitution of the cerebellum was noted. Patients with PFEAC might develop a Chiari I malformation and this might be treated with shunting of the PFEAC alone.

RMND5 from Xenopus laevis is an E3 ubiquitin-ligase and functions in early embryonic forebrain development.

PubMed

Pfirrmann, Thorsten; Villavicencio-Lorini, Pablo; Subudhi, Abinash K; Menssen, Ruth; Wolf, Dieter H; Hollemann, Thomas

2015-01-01

In Saccharomyces cerevisiae the Gid-complex functions as an ubiquitin-ligase complex that regulates the metabolic switch between glycolysis and gluconeogenesis. In higher organisms six conserved Gid proteins form the CTLH protein-complex with unknown function. Here we show that Rmnd5, the Gid2 orthologue from Xenopus laevis, is an ubiquitin-ligase embedded in a high molecular weight complex. Expression of rmnd5 is strongest in neuronal ectoderm, prospective brain, eyes and ciliated cells of the skin and its suppression results in malformations of the fore- and midbrain. We therefore suggest that Xenopus laevis Rmnd5, as a subunit of the CTLH complex, is a ubiquitin-ligase targeting an unknown factor for polyubiquitination and subsequent proteasomal degradation for proper fore- and midbrain development.

Flapping wing aerodynamics: from insects to vertebrates.

PubMed

Chin, Diana D; Lentink, David

2016-04-01

More than a million insects and approximately 11,000 vertebrates utilize flapping wings to fly. However, flapping flight has only been studied in a few of these species, so many challenges remain in understanding this form of locomotion. Five key aerodynamic mechanisms have been identified for insect flight. Among these is the leading edge vortex, which is a convergent solution to avoid stall for insects, bats and birds. The roles of the other mechanisms - added mass, clap and fling, rotational circulation and wing-wake interactions - have not yet been thoroughly studied in the context of vertebrate flight. Further challenges to understanding bat and bird flight are posed by the complex, dynamic wing morphologies of these species and the more turbulent airflow generated by their wings compared with that observed during insect flight. Nevertheless, three dimensionless numbers that combine key flow, morphological and kinematic parameters - the Reynolds number, Rossby number and advance ratio - govern flapping wing aerodynamics for both insects and vertebrates. These numbers can thus be used to organize an integrative framework for studying and comparing animal flapping flight. Here, we provide a roadmap for developing such a framework, highlighting the aerodynamic mechanisms that remain to be quantified and compared across species. Ultimately, incorporating complex flight maneuvers, environmental effects and developmental stages into this framework will also be essential to advancing our understanding of the biomechanics, movement ecology and evolution of animal flight. © 2016. Published by The Company of Biologists Ltd.

Genomic analysis of the Pacific oyster (Crassostrea gigas) reveals possible conservation of vertebrate sex determination in a mollusc.

PubMed

Zhang, Na; Xu, Fei; Guo, Ximing

2014-09-11

Despite the prevalence of sex in animal kingdom, we have only limited understanding of how sex is determined and evolved in many taxa. The mollusc Pacific oyster Crassostrea gigas exhibits complex modes of sexual reproduction that consists of protandric dioecy, sex change, and occasional hermaphroditism. This complex system is controlled by both environmental and genetic factors through unknown molecular mechanisms. In this study, we investigated genes related to sex-determining pathways in C. gigas through transcriptome sequencing and analysis of female and male gonads. Our analysis identified or confirmed novel homologs in the oyster of key sex-determining genes (SoxH or Sry-like and FoxL2) that were thought to be vertebrate-specific. Their expression profile in C. gigas is consistent with conserved roles in sex determination, under a proposed model where a novel testis-determining CgSoxH may serve as a primary regulator, directly or indirectly interacting with a testis-promoting CgDsx and an ovary-promoting CgFoxL2. Our findings plus previous results suggest that key vertebrate sex-determining genes such as Sry and FoxL2 may not be inventions of vertebrates. The presence of such genes in a mollusc with expression profiles consistent with expected roles in sex determination suggest that sex determination may be deeply conserved in animals, despite rapid evolution of the regulatory pathways that in C. gigas may involve both genetic and environmental factors. Copyright © 2014 Zhang et al.

Genomic Analysis of the Pacific Oyster (Crassostrea gigas) Reveals Possible Conservation of Vertebrate Sex Determination in a Mollusc

PubMed Central

Zhang, Na; Xu, Fei; Guo, Ximing

2014-01-01

Despite the prevalence of sex in animal kingdom, we have only limited understanding of how sex is determined and evolved in many taxa. The mollusc Pacific oyster Crassostrea gigas exhibits complex modes of sexual reproduction that consists of protandric dioecy, sex change, and occasional hermaphroditism. This complex system is controlled by both environmental and genetic factors through unknown molecular mechanisms. In this study, we investigated genes related to sex-determining pathways in C. gigas through transcriptome sequencing and analysis of female and male gonads. Our analysis identified or confirmed novel homologs in the oyster of key sex-determining genes (SoxH or Sry-like and FoxL2) that were thought to be vertebrate-specific. Their expression profile in C. gigas is consistent with conserved roles in sex determination, under a proposed model where a novel testis-determining CgSoxH may serve as a primary regulator, directly or indirectly interacting with a testis-promoting CgDsx and an ovary-promoting CgFoxL2. Our findings plus previous results suggest that key vertebrate sex-determining genes such as Sry and FoxL2 may not be inventions of vertebrates. The presence of such genes in a mollusc with expression profiles consistent with expected roles in sex determination suggest that sex determination may be deeply conserved in animals, despite rapid evolution of the regulatory pathways that in C. gigas may involve both genetic and environmental factors. PMID:25213692

Depdc5 knockdown causes mTOR-dependent motor hyperactivity in zebrafish.

PubMed

de Calbiac, Hortense; Dabacan, Adriana; Marsan, Elise; Tostivint, Hervé; Devienne, Gabrielle; Ishida, Saeko; Leguern, Eric; Baulac, Stéphanie; Muresan, Raul C; Kabashi, Edor; Ciura, Sorana

2018-05-01

DEPDC5 was identified as a major genetic cause of focal epilepsy with deleterious mutations found in a wide range of inherited forms of focal epilepsy, associated with malformation of cortical development in certain cases. Identification of frameshift, truncation, and deletion mutations implicates haploinsufficiency of DEPDC5 in the etiology of focal epilepsy. DEPDC5 is a component of the GATOR1 complex, acting as a negative regulator of mTOR signaling. Zebrafish represents a vertebrate model suitable for genetic analysis and drug screening in epilepsy-related disorders. In this study, we defined the expression of depdc5 during development and established an epilepsy model with reduced Depdc5 expression. Here we report a zebrafish model of Depdc5 loss-of-function that displays a measurable behavioral phenotype, including hyperkinesia, circular swimming, and increased neuronal activity. These phenotypic features persisted throughout embryonic development and were significantly reduced upon treatment with the mTORC1 inhibitor, rapamycin, as well as overexpression of human WT DEPDC5 transcript. No phenotypic rescue was obtained upon expression of epilepsy-associated DEPDC5 mutations (p.Arg487* and p.Arg485Gln), indicating that these mutations cause a loss of function of the protein. This study demonstrates that Depdc5 knockdown leads to early-onset phenotypic features related to motor and neuronal hyperactivity. Restoration of phenotypic features by WT but not epilepsy-associated Depdc5 mutants, as well as by mTORC1 inhibition confirm the role of Depdc5 in the mTORC1-dependent molecular cascades, defining this pathway as a potential therapeutic target for DEPDC5 -inherited forms of focal epilepsy.

A regional survey of malformed frogs in Minnesota (USA) (Minnesota malformed frogs).

PubMed

Vandenlangenberg, Susan M; Canfield, Jeffrey T; Magner, Joseph A

2003-02-01

In late 1995, school children discovered malformed frogs in a south central Minnesota pond. Press coverage resulted in numerous citizen reports of frog malformation across Minnesota in 1996. After some initial site investigation, 3 affected frog sites and 4 nearby reference sites were selected for more detailed evaluation. Field biologists made 89 visits to study sites beginning spring 1997 through fall 1999 to examine the number and type of frog malformations. Over 5,100 Leopard frogs (Rana pipiens) were captured and examined at all study sites. Water elevations and associated littoral inundation were recorded from 1997-2000. Results indicate that malformation occurred at all study sites above historical background levels. Rana pipiens malformation across all sites over three seasons averaged 7.9% and ranged from 0 to 7% at reference sites and 4 to 23% at affected sites. At one northern Minnesota site, mink frog (Rana septentrionalis) malformation was 75% in 1998. A site characteristic common to the most affected sites was an elastic zone of littoral inundation. Climate driven hydrologic variation likely influenced water depth and associated breeding locations.

Congenital heart defects and extracardiac malformations.

PubMed

Rosa, Rosana Cardoso M; Rosa, Rafael Fabiano M; Zen, Paulo Ricardo G; Paskulin, Giorgio Adriano

2013-06-01

To review the association between congenital heart defects and extracardiac malformations. Scientific articles were searched in the Medline, Lilacs, and SciELO databases, using the descriptors "congenital heart disease," "congenital heart defects," "congenital cardiac malformations," "extracardiac defects," and "extracardiac malformations." All case series that specifically explored the association between congenital heart defects and extracardiac malformations were included. Congenital heart diseases are responsible for about 40% of birth defects, being one of the most common and severe malformations. Extracardiac malformations are observed in 7 to 50% of the patients with congenital heart disease, bringing a greater risk of comorbidity and mortality and increasing the risks related to heart surgery. Different studies have attempted to assess the presence of extracardiac abnormalities in patients with congenital heart disease. Among the changes described, those of the urinary tract are more often reported. However, no study has evaluated all patients in the same way. Extracardiac abnormalities are frequent among patients with congenital heart disease, and patients with these alterations may present an increased risk of morbimortality. Therefore, some authors have been discussing the importance and cost-effectiveness of screening these children for other malformations by complementary exams.

[Poland'syndrome and hand's malformations: about a clinic series of 37 patients].

PubMed

Foucras, L; Grolleau, J L; Chavoin, J P

2005-04-01

Poland's syndrome is a rare malformation which associates thoracic anomalies and anomalies of homolateral upper end. We wish to know the frequency of hand's malformations in this syndrome in our clinical experience. We have revised 37 patients who were seen initially for a thoracomammary anomaly. This clinical series from plastic surgery service of Toulouse has been revised to know the importance of hand's malformations. Hand's malformations in Poland's syndrome are rare in your study, they touch only 12% patients. We find only 4 malformations in 33 patients, four were lost. They were only females, we find three brachymesophalangies and a major form. Hand's malformations in Poland's syndrome are less frequent than classically. There is no parallelism between gravity of thoracic malformation and that one of upper end. In this series, we find only one case with syndactyly; originally, Poland's syndrome was named < Poland's syndactyly >. Finally, we think that we can talk about Poland's syndrome without anomaly of homolateral upper end, the major element is musculary agenesia of sternocostal pectoralis major. The search of homolateral upper end has to be systematic in front of suspicious of Poland's syndrome.

Effect of 60Co gamma radiation on Biomphalaria glabrata (Mollusca, Gastropoda) embryos: mortality, malformation and hatching.

PubMed

Okazaki, K; Andrade Júnior, H F; Kawano, T

1996-08-01

A study was carried out on the radiosensitivity of Biomphalaria glabrata embryos submitted to doses of 5, 10, 15, 20 and 25 Gy of 60Co during the cleavage, blastula, gastrula, young trochophore and trochophore stages. Mortality, malformation and hatching were the parameters used to evaluate the damage induced by ionizing radiation. Estimated LD50 values (15 days) showed that the cleavage stage (4.3 Gy) was approximately four times more radiosensitive than the trochophore stage (17.0 Gy). Susceptibility to malformation induction was higher in the blastula, gastrula and young trochophore stages. Several types of morphogenetic malformations were observed, such as head malformations, exogastrulas, shell malformations, and embryos with everted stomodeum, with nonspecific malformations being the most frequent. The types of malformation induced by radiation probably are not radiation-specific and do not depend on the dose applied. The dose of 15 Gy was sufficient to greatly reduce the number of hatching snails regardless of the embryonic stage irradiated. We conclude that the effect of 60Co gamma radiation on B. glabrata embryos presented a specific pattern.

Pros, cons, and current indications of open craniotomy versus gamma knife in the treatment of arteriovenous malformations and the role of endovascular embolization.

PubMed

Surdell, Daniel L; Bhattacharjee, Sumon; Loftus, Christopher M

2002-06-01

The successful treatment of an intracranial arteriovenous malformation poses both technical and conceptual problems to the neurosurgeon. Treatment decisions are made in light of current understanding of the natural history of these lesions. It is important to understand the pros, cons and current indication of open craniotomy vs. gamma knife in the treatment of arteriovenous malformations and the role of endovascular embolization. Surgical removal of an arteriovenous malformation is indicated when the operative risk is less than the morbidity and mortality associated with its natural history. The treatment goal of complete angiographic obliteration of arteriovenous malformations is achieved most effectively by microneurosurgery in low-grade lesions. Large lesions frequently require a combination of embolization and microsurgery. Although recent advances in technology and medical management have allowed previously inoperable arteriovenous malformations to be surgically excised, there is still a small group of arteriovenous malformations that cannot be excised safely due to their size and location. Stereotactic radiosurgery is clearly an important adjunct in the multimodality treatment approach for large arteriovenous malformations. Endovascular embolization can potentially increase safety and efficacy in the treatment of arteriovenous malformations when applied to selective cases with well-defined treatment goals.

The impact of congenital cardiovascular malformations on the assessment and surgical management of infants with cleft lip and/or palate.

PubMed

Harry, Brian L; TeBockhorst, Seth; Deleyiannis, Frederic W-B

2013-05-01

The purpose of this study was to assess the cardiac evaluation of cleft lip and/or palate patients, characterize their cardiovascular malformations, and determine the impact of cardiovascular malformations on surgical management. A single-institution retrospective study of 329 consecutive cleft patients was performed. Cardiovascular malformations were categorized according to involvement of cardiac septa, vasculature, and valves. Their impact on the need for cardiac surgery, timing of cleft repair, need for subacute bacterial endocarditis (SBE) prophylaxis, and the perioperative experience was evaluated. Ten percent (33/329) of cleft patients had a cardiovascular malformation, and 3% underwent cardiac surgery prior to cleft repair. Malformations of the septa, vasculature, and valves were present in 9%, 6%, and 2% of cleft infants, respectively. Murmur as a sign of structural cardiovascular disease was 79% sensitive and 97% specific. Cleft palate repair was delayed by 2 months in patients with a cardiovascular malformation (P = .001). Subacute bacterial endocarditis prophylaxis was recommended, not recommended, or not specified by cardiology in 18%, 33%, and 48% of cleft patients with a cardiovascular malformation, respectively. Postoperative stay and surgical complications were not associated with cardiovascular malformation. Even in the absence of a murmur, echocardiographic screening should be considered in infants with nonspecific signs of cardiovascular disease. Greater awareness of the guidelines for SBE prophylaxis is needed. Most cleft patients with a cardiovascular malformation do not require cardiac surgery and do not experience an increased rate of complications associated with cleft surgery.

The archipelago of Fernando de Noronha: an intriguing malformed toad hotspot in South America.

PubMed

Toledo, Luís Felipe; Ribeiro, Ricardo S

2009-09-01

Malformed anurans raise concern among scientists, because deformities may relate to the recent global crisis among amphibian populations, although declining populations also may be associated with other causes (e.g., diseases, over-exploitation, and land use/land cover change). We examined a sample of toads (Rhinella jimi, Bufonidae) from an introduced population in the Archipelago of Fernando de Noronha, Brazil where malformations of anurans were thought to be high. Our sample of 159 specimens from the site revealed that 44.6% of all specimens had one or more malformations. Incidence of malformed toads on the mainland sites was substantially lower: 10.5% at Itamaracá, and 3.7% at Propriá. We describe the malformations observed, including six undescribed types of malformation of anurans, and we pose possible hypotheses to explain this high incidence of malformed toads. In addition to existing hypotheses, we suggest for the first time the hypothesis that lack of predation pressures contributes to numbers of malformed toads. We indicate the need of specific studies to understand the causes of malformations in the R. jimi population of Fernando de Noronha, which is thought to be extreme foci of malformed amphibians in the world. Our results may improve local conservation action plans as this is an alien population that may be affecting endemic fauna, and may affect populations in other parts of the world, because toad species of the genus Rhinella are recognized as exceptional colonizers. More importantly, unknown variables in these toads' environment are evidently affecting toads during development, which should be a concern for all species that inhabit the area, perhaps even humans.

Effect of Gastrointestinal Malformations on the Outcomes of Patients With Congenital Heart Disease.

PubMed

Mery, Carlos M; De León, Luis E; Rodriguez, J Rubén; Nieto, R Michael; Zhang, Wei; Adachi, Iki; Heinle, Jeffrey S; Kane, Lauren C; McKenzie, E Dean; Fraser, Charles D

2017-11-01

The goal of this study was to assess the effect of associated gastrointestinal malformations (GI) on the outcomes of patients undergoing congenital heart operations. Neonates and infants with thoracic (esophageal atresia, tracheoesophageal fistula) and abdominal (duodenal stenosis/atresia, imperforate anus, Hirschsprung disease) GI malformations undergoing congenital heart operations between 1995 and 2015 were included. Two control groups were created, one for each group. Patients were matched by diagnosis, procedure, history of prematurity, presence of genetic syndrome, and a propensity score including weight and year of operation. The cohort included 383 patients: 52 (14%) with thoracic GI malformations and 98 (25%) thoracic GI controls, 80 (21%) with abdominal GI malformations and 153 (40%) abdominal GI controls. Median follow-up was 6 years (range, 16 days to 20 years). Patients with thoracic GI malformations had longer length of stay (p < 0.001), longer intubation times (p = 0.002), and higher perioperative death (p = 0.015) than controls. There was a tendency for worse overall survival than controls, mainly explained by the higher risk of early death (p = 0.06). No difference was found in outcomes between patients with abdominal GI malformations and controls. Patients with thoracic GI malformations have worse perioperative outcomes than controls, but their long-term survival does not seem to be significantly different. Abdominal GI malformations do not have a significant effect on outcomes. The presence of GI malformations should likely not preclude patients from undergoing congenital heart operations, but careful family counseling is necessary, especially for thoracic GI malformations. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Congenital malformations in offspring of women with a history of malignancy.

PubMed

Sabeti Rad, Zahra; Friberg, Britt; Henic, Emir; Rylander, Lars; Ståhl, Olof; Källén, Bengt; Lingman, Göran

2017-02-15

Survival after malignancy has increased and the question of risks, including risk for congenital malformations for the offspring of these women has become important. Data on congenital malformations in such offspring are limited. We compared congenital malformation in offspring, born 1994 to 2011 of women with a history of malignancy (at least 1 year before delivery) with all other offspring. Adjustment for confounders was mainly made by Mantel-Haenszel methodology. Data were obtained by linkage between Swedish national health registers. We identified 71,954 (4.1%) infants with congenital malformation, of which 47,081 (2.7%) were relatively severe (roughly corresponding to major malformation). Among 7284 infants to women with a history of malignancy 204 relatively severe malformations were found (2.8%; odds ratio [OR] = 1.04; 95% confidence interval [CI], 0.91-1.20). After in vitro fertilization, the risk of a relatively severe malformation was significantly increased in women without a history of malignancy (OR = 1.31; 95% CI, 1.24-1.38) and still more in women with such a history (risk ratio = 1.85; 95% CI, 1.08-2.97). However, there were no significant differences neither, for any malformations (OR = 1.04; 95% CI, 0.92-1.16) nor for relatively severe malformations (OR = 1.04; 95% CI, 0.91-1.20), when comparing offspring only after maternal history of malignancy. No general increase in malformation rate was found in infants born to women with a history of malignancy. A previously known increased risk after in vitro fertilization was verified and it is possible that this risk is further augmented among infants born of women with a history of malignancy. Birth Defects Research 109:224-233, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Animal left-right asymmetry.

PubMed

Blum, Martin; Ott, Tim

2018-04-02

Symmetry is appealing, be it in architecture, art or facial expression, where symmetry is a key feature to finding someone attractive or not. Yet, asymmetries are widespread in nature, not as an erroneous deviation from the norm but as a way to adapt to the prevailing environmental conditions at a time. Asymmetries in many cases are actively selected for: they might well have increased the evolutionary fitness of a species. Even many single-celled organisms are built asymmetrically, such as the pear-shaped ciliate Paramecium, which may depend on its asymmetry to navigate towards the oxygen-richer surface of turbid waters, at least based on modeling. Everybody knows the lobster with its asymmetric pair of claws, the large crusher usually on the left and the smaller cutter on the right. Snail shells coil asymmetrically, as do the organs they house. Organ asymmetries are found throughout the animal kingdom, referring to asymmetric positioning, asymmetric morphology or both, with the vertebrate heart being an example for the latter. Functional asymmetries, such as that of the human brain with its localization of the language center in one hemisphere, add to the complexity of organ asymmetries and presumably played a decisive role for sociocultural evolution. The evolutionary origin of organ asymmetries may have been a longer than body length gut, which allows efficient retrieval of nutrients, and the need to stow a long gut in the body cavity in an orderly manner that ensures optimal functioning. Vertebrate organ asymmetries (situs solitus) are quite sophisticated: in humans, the apex of the asymmetrically built heart points to the left; the lung in turn, due to space restrictions, has fewer lobes on the left than on the right side (two versus three in humans), stomach and spleen are found on the left, the liver on the right, and small and large intestine coil in a chiral manner (Figure 1A). In very rare cases (1:10,000), the organ situs is inverted (situs inversus), while heterotaxia refers to another rare situation (about 1:1,000), in which subsets of organs show normal or aberrant positioning or morphology (Figure 1B). Individuals with situs solitus or situs inversus are healthy, whereas heterotaxia presents severe congenital malformations. Many human syndromes are known in which patients suffer from laterality defects, such as Katagener syndrome, in which the organ situs is inverted in one half of patients and males are sterile. Snail shells and vertebrate organs are examples of biased asymmetries with on average only one inversion in every 10,000 cases. Other asymmetries such as the coiling of the tails of piglets occur randomly with a 50:50 distribution. This primer exclusively deals with organ asymmetries in the animal kingdom, specifically with the mechanisms that ensure the development of biased asymmetries during embryogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

CONGENITAL HEART MALFORMATIONS IN NEWBORN BABIES WITH LOW BIRTH WEIGHT.

PubMed

Luca, Alina-Costina; Holoc, Andreea-Simona; Iordache, C

2015-01-01

Congenital heart malformations represent a public health problem, holding a significant percentage of the total of heart diseases. Beside the elevated frequency of the malformations, we also notice their occurrence in newborn babies with low birth weight, increasing, thus, the risk of complications and late therapeutic approach. The goal of the study was to highlight the general and particular aspects of cardiovascular malformations epidemiology in newborn babies with low weight at birth, the correlation of the malformations with implied genetic and environmental factors, assessing the complications and their procedures on the therapeutic management. Our study was performed on a group of 271 patients, hospitalized in the Department of Pediatric Cardiology of "Sf. Maria" Emergency Clinical Hospital for Children of Iasi, during January 2011-December 2013. The patients were assessed based on anamnesis, clinical, biological and imagistic exam. The study lot was divided according to the type of the structural defect: 95% of the patients were diagnosed with non-cyanogenic congenital heart malformations and 5% with cyanogenic congenital heart malformations. Regarding the patient's origin background, we notice an elevated frequency of the rural environment (71%). The incidence of the malformations was high in premature low birth weight (48%), followed by premature very low birth weight (22%). In evolution, congenital heart malformations often get more complicated heart failure, arterial hypertension and respiratory infections being most often met. Mortality was maximum in the first year of life, a third of the cases being associated with chromosomal malformations. Congenital heart malformations in newborn patients with low weight at birth represented an elevated percentage of 44.13% of the total of the cases hospitalized for cardiovascular diseases from the Department of Pediatric Cardiology of Iasi. Many cases were associated with other congenital malformations or different complications, being necessary an interdisciplinary collaboration to adequately monitor the anatom5ical and functional parameters and to ensure a somatic and mental development as normal as possible.

Complex mixtures of anti-androgens at concentrations below individual chemical effect levels produces reproductive tract malformations in the male rat

EPA Science Inventory

This product is a powerpoint presentation for use in two invited talks (webinars) as part of the CSS RAP. There is no abstract to attach as this is not a conference presentation and an abstract was not required or prepared. The CSS NPD talk will be August 14 and the CSS AOPDD We...

Candidate gene screen in the red flour beetle Tribolium reveals six3 as ancient regulator of anterior median head and central complex development.

PubMed

Posnien, Nico; Koniszewski, Nikolaus Dieter Bernhard; Hein, Hendrikje Jeannette; Bucher, Gregor

2011-12-01

Several highly conserved genes play a role in anterior neural plate patterning of vertebrates and in head and brain patterning of insects. However, head involution in Drosophila has impeded a systematic identification of genes required for insect head formation. Therefore, we use the red flour beetle Tribolium castaneum in order to comprehensively test the function of orthologs of vertebrate neural plate patterning genes for a function in insect head development. RNAi analysis reveals that most of these genes are indeed required for insect head capsule patterning, and we also identified several genes that had not been implicated in this process before. Furthermore, we show that Tc-six3/optix acts upstream of Tc-wingless, Tc-orthodenticle1, and Tc-eyeless to control anterior median development. Finally, we demonstrate that Tc-six3/optix is the first gene known to be required for the embryonic formation of the central complex, a midline-spanning brain part connected to the neuroendocrine pars intercerebralis. These functions are very likely conserved among bilaterians since vertebrate six3 is required for neuroendocrine and median brain development with certain mutations leading to holoprosencephaly.

Candidate Gene Screen in the Red Flour Beetle Tribolium Reveals Six3 as Ancient Regulator of Anterior Median Head and Central Complex Development

PubMed Central

Hein, Hendrikje Jeannette; Bucher, Gregor

2011-01-01

Several highly conserved genes play a role in anterior neural plate patterning of vertebrates and in head and brain patterning of insects. However, head involution in Drosophila has impeded a systematic identification of genes required for insect head formation. Therefore, we use the red flour beetle Tribolium castaneum in order to comprehensively test the function of orthologs of vertebrate neural plate patterning genes for a function in insect head development. RNAi analysis reveals that most of these genes are indeed required for insect head capsule patterning, and we also identified several genes that had not been implicated in this process before. Furthermore, we show that Tc-six3/optix acts upstream of Tc-wingless, Tc-orthodenticle1, and Tc-eyeless to control anterior median development. Finally, we demonstrate that Tc-six3/optix is the first gene known to be required for the embryonic formation of the central complex, a midline-spanning brain part connected to the neuroendocrine pars intercerebralis. These functions are very likely conserved among bilaterians since vertebrate six3 is required for neuroendocrine and median brain development with certain mutations leading to holoprosencephaly. PMID:22216011

Dandy-Walker Malformation Presenting with Psychological Manifestations.

PubMed

Rohanachandra, Yasodha Maheshi; Dahanayake, Dulangi Maneksha Amerasinghe; Wijetunge, Swarna

2016-01-01

Dandy-Walker malformation, which is a congenital malformation of the cerebellum, is documented in literature to be associated with psychotic symptoms, obsessive compulsive symptoms, mood symptoms, hyperactivity, and impulsive behavior. The pathogenesis of psychiatric symptoms in Dandy-Walker malformation is thought to be due to disruption of the corticocerebellar tracts, resulting in what is known as cerebellar cognitive affective syndrome. We present a case of Dandy-Walker malformation presenting with psychiatric symptoms. This case highlights the necessity to be aware of psychiatric manifestations of cerebellar disease as it has an impact on the diagnosis and treatment.

Neuro-ophthalmology of type 1 Chiari malformation

PubMed Central

Shaikh, Aasef G.; Ghasia, Fatema F.

2016-01-01

Chiari malformation is a congenital deformity leading to herniation of cerebellar tonsils. Headache is a typical symptom of this condition, but patients with Chiari malformation often present with double vision and vertigo. Examination of eye movements in such patients often reveals nystagmus and strabismus. Eye movement deficits in the context of typical symptomatic presentation are critical clinical markers for the diagnosis of Chiari malformation. We will review eye movement deficits that seen in patients with type 1 Chiari malformation. We will then discuss the underlying pathophysiology and therapeutic options for such deficits. PMID:26843890

Dietary fatty acids and inflammation in the vertebral column of Atlantic salmon, Salmo salar L., smolts: a possible link to spinal deformities.

PubMed

Gil Martens, L; Lock, E J; Fjelldal, P G; Wargelius, A; Araujo, P; Torstensen, B E; Witten, P E; Hansen, T; Waagbø, R; Ørnsrud, R

2010-12-01

Vegetable oils (Vo) are an alternative to fish oil (Fo) in aquaculture feeds. This study aimed to evaluate the effect of dietary soybean oil (Vo diet), rich in linoleic acid, and of dietary fish oil (Fo diet) on the development of spinal deformities under bacterial lipopolysaccharide (LPS)-induced chronic inflammation conditions in Atlantic salmon, Salmo salar L. Fish [25 g body weight (BW)] were fed the experimental diets for 99 days. On day 47 of feeding (40 g BW), fish were subjected to four experimental regimes: (i) intramuscular injections with LPS, (ii) sham-injected phosphate-buffered saline (PBS), (iii) intraperitoneally injected commercial oil adjuvant vaccine, or (iv) no treatment. The fish continued under a common feeding regime in sea water for 165 more days. Body weight was temporarily higher in the Vo group than in the Fo group prior to immunization and was also affected by the type of immunization. At the end of the trial, no differences were seen between the dietary groups. The overall prevalence of spinal deformities was approximately 14% at the end of the experiment. The Vo diet affected vertebral shape but did not induce spinal deformities. In groups injected with LPS and PBS, spinal deformities ranged between 21% and 38%, diet independent. Deformed vertebrae were located at or in proximity to the injection point. Assessment of inflammatory markers revealed high levels of plasma prostaglandin E₂ (PGE₂) in the Vo-fed and LPS-injected groups, suggesting an inflammatory response to LPS. Cyclooxigenase 2 (COX-2) mRNA expression in bone was higher in fish fed Fo compared to Vo-fed fish. Gene expression of immunoglobulin M (IgM) was up-regulated in bone of all LPS-injected groups irrespective of dietary oil. In conclusion, the study suggests that Vo is not a risk factor for the development of inflammation-related spinal deformities. At the same time, we found evidence that localized injection-related processes could trigger the development of vertebral body malformations. © 2010 Blackwell Publishing Ltd.

Contribution of Rare Copy Number Variants to Isolated Human Malformations

PubMed Central

Serra-Juhé, Clara; Rodríguez-Santiago, Benjamín; Cuscó, Ivon; Vendrell, Teresa; Camats, Núria; Torán, Núria; Pérez-Jurado, Luis A.

2012-01-01

Background Congenital malformations are present in approximately 2–3% of liveborn babies and 20% of stillborn fetuses. The mechanisms underlying the majority of sporadic and isolated congenital malformations are poorly understood, although it is hypothesized that the accumulation of rare genetic, genomic and epigenetic variants converge to deregulate developmental networks. Methodology/Principal Findings We selected samples from 95 fetuses with congenital malformations not ascribed to a specific syndrome (68 with isolated malformations, 27 with multiple malformations). Karyotyping and Multiplex Ligation-dependent Probe Amplification (MLPA) discarded recurrent genomic and cytogenetic rearrangements. DNA extracted from the affected tissue (46%) or from lung or liver (54%) was analyzed by molecular karyotyping. Validations and inheritance were obtained by MLPA. We identified 22 rare copy number variants (CNV) [>100 kb, either absent (n = 7) or very uncommon (n = 15, <1/2,000) in the control population] in 20/95 fetuses with congenital malformations (21%), including 11 deletions and 11 duplications. One of the 9 tested rearrangements was de novo while the remaining were inherited from a healthy parent. The highest frequency was observed in fetuses with heart hypoplasia (8/17, 62.5%), with two events previously related with the phenotype. Double events hitting candidate genes were detected in two samples with brain malformations. Globally, the burden of deletions was significantly higher in fetuses with malformations compared to controls. Conclusions/Significance Our data reveal a significant contribution of rare deletion-type CNV, mostly inherited but also de novo, to human congenital malformations, especially heart hypoplasia, and reinforce the hypothesis of a multifactorial etiology in most cases. PMID:23056206

In vitro fertilization (IVF) in Sweden: risk for congenital malformations after different IVF methods.

PubMed

Källén, Bengt; Finnström, Orvar; Nygren, Karl Gösta; Olausson, Petra Otterblad

2005-03-01

The possible excess of congenital malformations in infants born after in vitro fertilization (IVF) has been much discussed in the literature, with controversial conclusions. This population based study is aimed at analyzing the presence of congenital malformations in a large group of infants born after IVF and to compare malformation risk both with that of all infants born and according to IVF method used. Infants born after IVF during the period 1982-2001 were ascertained from all IVF clinics in Sweden. The presence of congenital malformations was identified from three national health registers: the Swedish Medical Birth Register, the Swedish Registry of Congenital Malformations, and the Swedish Hospital Discharge Register. The IVF children were compared with all children born in Sweden during the same period and recorded in the Swedish Medical Birth Register. Among 16,280 IVF children (30% conceived after intracytoplasmatic sperm injection [ICSI]) a 42% excess of any congenital malformation was found, explainable by parental characteristics and in some cases by the high rate of multiple births. Among these children, 8% had a congenital malformation, and 5% had a relatively severe condition. For neural tube defects, choanal atresia, and alimentary tract atresia, an additional risk increase was seen. There was no difference in malformation rate according to IVF method except for an excess of hypospadias after ICSI. An increased risk for congenital malformations occurs after IVF, similar for the different IVF techniques used, and mainly a consequence of parental characteristics. A few specific conditions show an extra increase in risk. Copyright 2005 Wiley-Liss, Inc.

Structural basis for the Nanos-mediated recruitment of the CCR4-NOT complex and translational repression.

PubMed

Bhandari, Dipankar; Raisch, Tobias; Weichenrieder, Oliver; Jonas, Stefanie; Izaurralde, Elisa

2014-04-15

The RNA-binding proteins of the Nanos family play an essential role in germ cell development and survival in a wide range of metazoan species. They function by suppressing the expression of target mRNAs through the recruitment of effector complexes, which include the CCR4-NOT deadenylase complex. Here, we show that the three human Nanos paralogs (Nanos1-3) interact with the CNOT1 C-terminal domain and determine the structural basis for the specific molecular recognition. Nanos1-3 bind CNOT1 through a short CNOT1-interacting motif (NIM) that is conserved in all vertebrates and some invertebrate species. The crystal structure of the human Nanos1 NIM peptide bound to CNOT1 reveals that the peptide opens a conserved hydrophobic pocket on the CNOT1 surface by inserting conserved aromatic residues. The substitutions of these aromatic residues in the Nanos1-3 NIMs abolish binding to CNOT1 and abrogate the ability of the proteins to repress translation. Our findings provide the structural basis for the recruitment of the CCR4-NOT complex by vertebrate Nanos, indicate that the NIMs are the major determinants of the translational repression mediated by Nanos, and identify the CCR4-NOT complex as the main effector complex for Nanos function.

Bendectin and human congenital malformations.

PubMed

Shiono, P H; Klebanoff, M A

1989-08-01

The relationship between Bendectin exposure during the first trimester of pregnancy and the occurrence of congenital malformations was prospectively studied in 31,564 newborns registered in the Northern California Kaiser Permanente Birth Defects Study. The odds ratio for any major malformation and Bendectin use was 1.0 (95% confidence interval 0.8-1.4). There were 58 categories of congenital malformations; three of them were statistically associated with Bendectin exposure (microcephaly--odds ratio = 5.3, 95% confidence interval = 1.8-15.6; congenital cataract--odds ratio = 5.3, 95% confidence interval = 1.2-24.3; lung malformations (ICD-8 codes 484.4-484.8)--odds ratio = 4.6, 95% confidence interval = 1.9-10.9). This is exactly the number of associations that would be expected by chance. An independent study (the Collaborative Perinatal Project) was used to determine whether vomiting during pregnancy in the absence of Bendectin use was associated with these three malformations. Two of the three (microcephaly and cataract) had strong positive associations with vomiting in the absence of Bendectin use. We conclude that there is no increase in the overall rate of major malformations after exposure to Bendectin and that the three associations found between Bendectin and individual malformations are unlikely to be causal.

Vascular anomalies of the head and neck: a review of genetics.

PubMed

Yadav, Prashant; De Castro, Dawn K; Waner, Milton; Meyer, Lutz; Fay, Aaron

2013-01-01

Vascular anomalies comprise malformations, hemangiomas, and rare tumors. The commonality among these lesions is their origin in vascular endothelia. Most occur sporadically, but occasional inheritance is observed and thus allows genetic research and insight into etiology. This review highlights those vascular anomalies in which genetic inheritance has been demonstrated. A comprehensive literature search was performed on PubMed. Fifty-five full-length articles were reviewed. Five categories of vascular anomalies with patterned inheritance were identified: arteriovenous malformation (AVM), capillary malformation (CM), lymphatic malformation (LM), venous malformation (VM), and infantile hemangioma (IH). Capillary and arteriovenous malformation subtypes are associated with a RASA-1 gene mutation and show autosomal dominant inheritance. VEGFR3 mutations have been associated with generalized forms of LM and lymphedema. Mutations in TIE2/TEK genes cause inherited forms of venous malformations also with autosomal dominant inheritance. Familial clustering and atopic disease are associated with infantile hemangioma, and gene expression varies with the developmental stage of these lesions. Most vascular anomalies occur sporadically, but several genes and genetic disorders have been associated with them. Specific forms of capillary malformation appear to be most convincingly associated with genomic errors. Further research promises new insights into the development of this diverse group of disorders.

Intracranial Hypertension in a Patient with a Chiari Malformation Accompanied by Hyperthyroidism.

PubMed

Pang, Chang Hwan; Lee, Soo Eon; Kim, Chi Heon; Chung, Chun Kee

2015-09-01

The Chiari malformation is an infrequently detected congenital anomaly characterized by the downward displacement of the cerebellum with a tonsillar herniation below the foramen magnum that may be accompanied by either syringomyelia or hydrocephalus. Surgery, such as foramen magnum decompression, is indicated for a symptomatic Chiari malformation, although an incidental lesion may be followed-up without further treatment. Infrequently, increased intracranial pressure emerges due to hyperthyroidism. A nineteen-year-old girl visited our outpatient clinic presented with a headache, nausea and vomiting. A brain and spinal magnetic resonance image study (MRI) indicated that the patient had a Chiari I malformation without syringomyelia or hydrocephalus. An enlarged thyroid gland was detected on a physical examination, and serum markers indicated Graves' disease. The patient started anti-hyperthyroid medical treatment. Subsequently, the headache disappeared after the medical treatment of hyperthyroidism without surgical intervention for the Chiari malformation. A symptomatic Chiari malformation is indicated for surgery, but a surgeon should investigate other potential causes of the symptoms of the Chiari malformation to avoid unnecessary surgery.

Equilibrium and Orientation in Cephalopods.

ERIC Educational Resources Information Center

Budelmann, Bernd-Ulrich

1980-01-01

Describes the structure of the equilibrium receptor system in cephalopods, comparing it to the vertebrate counterpart--the vestibular system. Relates the evolution of this complex system to the competition of cephalopods with fishes. (CS)

[Venous and arteriovenous malformations in the head and neck region. Therapeutic options and challenges].

PubMed

Eivazi, B; Werner, J A

2014-01-01

Venous malformations are the prototype low-flow malformations in the head and neck region. Arteriovenous malformations (AVM) represent the main high-flow malformations. In recent years it has been possible to significantly optimize the therapeutic options for venous malformations. In addition to conventional surgery, laser treatment and sclerotherapy have become established techniques and the importance of embolization with new alcohol-based materials is increasing. AVM are progressive and destructive diseases. Therapy of choice is usually a combined treatment comprising embolization and surgical removal of the arteriovenous nidus. This curative approach is usually possible if diagnosis is made at an early stage. Incomplete embolization or sole ligation of the arterial supply causes progression. There is a clear need for improved therapeutic methods and pharmacotherapeutic approaches.

Acquired Uterine Arteriovenous Malformation and Retained Placenta Increta.

PubMed

Roach, Michelle K; Thomassee, May S

2015-09-01

Uterine arteriovenous malformations are rare and have been reported to occur after uterine trauma (eg, surgery, gestational trophoblastic disease, malignancy). A 33-year-old woman, gravida 3 para 3, presented 4 weeks post-cesarean delivery with episodic profuse vaginal bleeding. Pelvic ultrasonography and magnetic resonance imaging revealed a left uterine arteriovenous malformation. After consideration of all treatment options, total laparoscopic hysterectomy was performed. Acquired uterine arteriovenous malformations and placental ingrowth into the myometrium are increasingly reported after surgical uterine procedures. This case of a postpartum patient with both uterine arteriovenous malformation and retained placenta increta suggests a correlation between the two complications.

Dandy-Walker Malformation Presenting with Psychological Manifestations

PubMed Central

Dahanayake, Dulangi Maneksha Amerasinghe

2016-01-01

Dandy-Walker malformation, which is a congenital malformation of the cerebellum, is documented in literature to be associated with psychotic symptoms, obsessive compulsive symptoms, mood symptoms, hyperactivity, and impulsive behavior. The pathogenesis of psychiatric symptoms in Dandy-Walker malformation is thought to be due to disruption of the corticocerebellar tracts, resulting in what is known as cerebellar cognitive affective syndrome. We present a case of Dandy-Walker malformation presenting with psychiatric symptoms. This case highlights the necessity to be aware of psychiatric manifestations of cerebellar disease as it has an impact on the diagnosis and treatment. PMID:27493822

[Advances in genetics of congenital malformation of external and middle ear].

PubMed

Wang, Dayong; Wang, Qiuju

2013-05-01

Congenital malformation of external and middle ear is a common disease in ENT department, and the incidence of this disease is second only to cleft lip and palate in the whole congenital malformations of the head and face. The external and middle ear malformations may occur separately, or as an important ear symptom of the systemic syndrome. We systematically review and analysis the genetic research progress of congenital malformation of external and middle ear, which would be helpful to understand the mechanism of external and middle ear development, and to provide clues for the further discovery of new virulence genes.

Embryonic expression of endothelins and their receptors in lamprey and frog reveals stem vertebrate origins of complex Endothelin signaling

PubMed Central

Square, Tyler; Jandzik, David; Cattell, Maria; Hansen, Andrew; Medeiros, Daniel Meulemans

2016-01-01

Neural crest cells (NCCs) are highly patterned embryonic cells that migrate along stereotyped routes to give rise to a diverse array of adult tissues and cell types. Modern NCCs are thought to have evolved from migratory neural precursors with limited developmental potential and patterning. How this occurred is poorly understood. Endothelin signaling regulates several aspects of NCC development, including their migration, differentiation, and patterning. In jawed vertebrates, Endothelin signaling involves multiple functionally distinct ligands (Edns) and receptors (Ednrs) expressed in various NCC subpopulations. To test the potential role of endothelin signaling diversification in the evolution of modern, highly patterned NCC, we analyzed the expression of the complete set of endothelin ligands and receptors in the jawless vertebrate, the sea lamprey (Petromyzon marinus). To better understand ancestral features of gnathostome edn and ednr expression, we also analyzed all known Endothelin signaling components in the African clawed frog (Xenopus laevis). We found that the sea lamprey has a gnathsotome-like complement of edn and ednr duplicates, and these genes are expressed in patterns highly reminiscent of their gnathostome counterparts. Our results suggest that the duplication and specialization of vertebrate Endothelin signaling coincided with the appearance of highly patterned and multipotent NCCs in stem vertebrates. PMID:27677704

Elongation Factor-1a is a novel protein associated with host cell invasion and a potential protective antigen of Cryptosporidium parvum*

USDA-ARS?s Scientific Manuscript database

The phylum Apicomplexa comprises obligate intracellular parasites that infect vertebrates. All invasive forms of Apicomplexa possess a unique complex of organelles at the anterior end, referred to as the apical complex, which is involved in host cell invasion. Previously, we generated the chicken m...

Congenital Diaphragmatic Hernia: The Side of Diaphragmatic Defect and Associated Nondiaphragmatic Malformations.

PubMed

Grizelj, Ruža; Bojanić, Katarina; Vuković, Jurica; Weingarten, Toby N; Schroeder, Darrell R; Sprung, Juraj

2017-07-01

Background  Congenital diaphragmatic hernia (CDH) has different clinical presentations depending on whether it is right sided (R-CDH) or left sided (L-CDH). Some have suggested that L-CDH and R-CDH may represent different syndromic phenotypes. This theory would be indirectly supported if different nondiaphragmatic anomalies were associated with laterality. We assessed whether CDH laterality is associated with specific types of nondiaphragmatic anomalies. Methods  Cases of CDH were retrospectively identified from five centers, and associated congenital anomalies, prenatal diagnosis, demographics, birth characteristics, and side of the CDH were analyzed. CDH characteristics were summarized according to the absence (isolated) or presence (complex) of nondiaphragmatic malformations. Results  Among 228 neonates with CDH, 140 (61%) had isolated CDH and 88 (39%) had complex CDH. Complex CDH was significantly associated with being small for gestational age (odds ratio [95% confidence interval, CI]: 8.3 [1.9-35.7]; p  = 0.005) and having L-CDH (odds ratio [95% CI]: 3.6 [1.5-8.9]; p  = 0.005). The overall proportion with anomalies differed by side (42% for L-CDH, 23% for R-CDH; p  = 0.02), but the rates of anomalies in specific organ systems did not differ. Conclusion  The rate of associated nondiaphragmatic anomalies by specific organ system did not differ between L-CDH and R-CDH, which suggests that they represent the same phenotypic entity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A unique case of penetrating neck and cervical spine trauma resulting in vertebral artery transection and internal carotid artery laceration.

PubMed

Marston, Alexander P; Montenegro, Monique M; Oldenburg, Michael S; Thom, Joshua T; Driscoll, Colin L W

2016-01-01

Describe the presentation and treatment of a patient who suffered a penetrating cervical trauma resulting in occlusion of the vertebral and internal carotid arteries. The electronic medical record was used to collect information pertaining to the patient's clinical history. A 20-year-old male suffered a unique penetrating neck injury resulting in simultaneous injuries to the internal carotid and vertebral arteries as demonstrated by pre-operative angiography. Combined endovascular and open surgical approaches were utilized to successfully manage the vascular injuries prior to foreign body extraction. Complex penetrating cervical trauma is best managed with a multidisciplinary and multimodality approach. In appropriately selected patients, pre-operative angiography is a critical diagnostic modality that can prevent life-threatening hemorrhage following foreign body extraction. Copyright © 2016 Elsevier Inc. All rights reserved.

Arm injury produces long-term behavioral and neural hypersensitivity in octopus.

PubMed

Alupay, Jean S; Hadjisolomou, Stavros P; Crook, Robyn J

2014-01-13

Cephalopod molluscs are the most neurally and behaviorally complex invertebrates, with brains rivaling those of some vertebrates in size and complexity. This has fostered the opinion that cephalopods, particularly octopuses, may experience vertebrate-like pain when injured. However, it is not known whether octopuses possess nociceptors or if their somatic sensory neurons exhibit sensitization after injury. Here we show that the octopus Abdopus aculeatus expresses nocifensive behaviors including arm autotomy, and displays marked neural hyperexcitability both in injured and uninjured arms for at least 24h after injury. These findings do not demonstrate that octopuses experience pain-like states; instead they add to the minimal existing literature on how cephalopods receive, process, and integrate noxious sensory information, potentially informing and refining regulations governing use of cephalopods in scientific research. Published by Elsevier Ireland Ltd.

Unusual Discovery after an Examination for Abdominal Pain: Abernethy 1b Malformation and Liver Adenomatosis. A Case Report.

PubMed

Chira, Romeo Ioan; Calauz, Adriana; Manole, Simona; Valean, Simona; Mircea, Petru Adrian

2017-03-01

Congenital extrahepatic portosystemic shunt (Abernethy malformation) is a rare condition characterized by developmental abnormalities of the portal venous system resulting in the diversion of the portal blood from the liver to the systemic venous system through a complete or partial shunt of the portomesenteric blood. We report the case of an 18 year-old female examined for abdominal pain, presenting cholestasis syndrome and an elevated serum aspartate aminotransferase level. Liver ultrasound examination revealed the absence of the portal vein with a complete extrahepatic shunt of the portal blood, multiple focal liver lesions, and multiple associated vascular anomalies. A surgical portosystemic shunt and a secondary portosystemic shunt due to portal vein thrombosis were excluded, enabling the diagnosis of a congenital portosystemic shunt. A complex investigation also discovered bone anomalies, and the liver biopsy of the dominant focal lesion revealed adenoma. On a short-term follow-up under hepatoprotective medication, the biochemical parameters improved mildly; however, the size of the main focal lesion increased. Congenital absence of the portal vein often remains an incidental diagnosis. In experienced hands, ultrasonography can diagnose it, but a comprehensive thoraco-abdominal evaluation is compulsory, considering the many potential associated anomalies. In these patients, development of adenomatous liver lesions secondary to Abernethy type Ib malformation represents an indication for liver transplantation.

[Microtia-atresia: clinical, genetic and genomic aspects].

PubMed

Aguinaga-Ríos, Mónica; Frías, Sara; Arenas-Aranda, Diego J; Morán-Barroso, Verónica Fabiola

Mexico has a prevalence of microtia of 7.37/10,000 (newborns), 3 times higher than the prevalence reported in other populations (USA 2-3/10,000). Microtia is defined as a congenital malformation of the external ear characterized by a small auricular lobe with an abnormal shape. It is more often unilateral and on the right side. Males are more frequently affected than females. It can occur as an isolated defect or can be associated with other abnormalities such as stenosis of the external auditory canal. In three of the main pediatric hospitals in Mexico, microtia is among the most important causes of attendance in the Genetics Department. Microtia-atresia must be considered as a major malformation with important repercussions in hearing function requiring multidisciplinary medical care in order to limit the disability associated and to provide genetic counseling. Its etiology is complex. Only in a minor number of cases it has been possible to identify a main genetic component (as in monogenic presentations) or a main environmental cause (as in fetal alcohol syndrome or pregestational diabetes). In most cases this malformation is multifactorial. Due to the relevance that the frequency of microtia atresia has in different health services in Mexico, it is important that all medical professionals are aware of its clinical, molecular and inherited characteristics. Copyright © 2014 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Unique Features of Fish Immune Repertoires: Particularities of Adaptive Immunity Within the Largest Group of Vertebrates

PubMed Central

Sunyer, Oriol J.

2016-01-01

Fishes (i.e., teleost fishes) are the largest group of vertebrates. Although their immune system is based on the fundamental receptors, pathways, and cell types found in all groups of vertebrates, fishes show a diversity of particular features that challenge some classical concepts of immunology. In this chapter, we discuss the particularities of fish immune repertoires from a comparative perspective. We examine how allelic exclusion can be achieved when multiple Ig loci are present, how isotypic diversity and functional specificity impact clonal complexity, how loss of the MHC class II molecules affects the cooperation between T and B cells, and how deep sequencing technologies bring new insights about somatic hypermutation in the absence of germinal centers. The unique coexistence of two distinct B-cell lineages respectively specialized in systemic and mucosal responses is also discussed. Finally, we try to show that the diverse adaptations of immune repertoires in teleosts can help in understanding how somatic adaptive mechanisms of immunity evolved in parallel in different lineages across vertebrates. PMID:26537384

Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations

PubMed Central

Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J; Seely, Ellen W; Mogun, Helen; Dejene, Sara Z; Fischer, Michael A; Friedman, Alexander M; Hernandez-Diaz, Sonia; Huybrechts, Krista F

2016-01-01

Objective To examine the association between first-trimester angiotensin-converting enzyme (ACE) inhibitor exposure and the risk for overall major congenital, cardiac, and central nervous system (CNS) malformations. Methods We used a cohort of completed pregnancies linked to liveborn infants derived from Medicaid claims from 2000 to 2010. We examined the risk of malformations associated with first-trimester exposure to an ACE inhibitor. Propensity score based methods were used to control for potential confounders including maternal demographics, medical conditions, exposure to other medications, and measures of health care utilization. Results The cohort included 1,333,624 pregnancies, of which 4,107 (0.31%) were exposed to ACE inhibitors during the first trimester. The prevalence of overall malformations in the ACE inhibitor–exposed was 5.9% versus 3.3% in the unexposed (unadjusted relative risk (RR), 1.82; 95% confidence interval (CI) 1.61 to 2.06), of cardiac malformations was 3.4% versus 1.2% (RR 2.95; 95% CI 2.50 to 3.47), and of CNS malformations was 0.27% versus 0.18% (RR 1.46; 95% CI 0.81 to 2.64). After restricting the cohort to pregnancies complicated by chronic hypertension (both exposed and unexposed) and accounting for other confounding factors, there was no significant increase in the risk for any of the outcomes assessed. Relative risks associated with first-trimester ACE inhibitor exposure were 0.89 (95% CI 0.75 to 1.06) for overall malformations, 0.95 (95% CI 0.75 to 1.21) for cardiac malformations, and 0.54 (95% CI 0.26 to 1.11) for CNS malformations. Conclusions After accounting for confounders, among women with hypertension, exposure to ACE inhibitors during the first trimester was not associated with an increased risk of major congenital malformations. PMID:27926639

Slide tracheoplasty outcomes in children with congenital pulmonary malformations.

PubMed

DeMarcantonio, Michael A; Hart, Catherine K; Yang, Christina J; Tabangin, Meredith; Rutter, Michael J; Bryant, Roosevelt; Manning, Peter B; de Alarcón, Alessandro

2017-06-01

Evaluate and compare surgical outcomes of slide tracheoplasty for the treatment of congenital tracheal stenosis in children with and without pulmonary malformations. Retrospective chart review at a tertiary care pediatric medical center. We identified patients with tracheal stenosis who underwent slide tracheoplasty from 2001 to 2014, and a subset of these patients who were diagnosed with congenital pulmonary malformations. Hospital course and preoperative and postoperative complications were recorded. One hundred thirty patients (18 with pulmonary malformations, 112 with normal pulmonary anatomy) were included. Pulmonary malformations included unilateral pulmonary agenesis (61%) and hypoplasia (39%). Children with pulmonary malformations had a greater median age compared to their normal lung anatomy counterparts. Preoperatively, patients with pulmonary malformations more frequently required preoperative mechanical ventilation (55.6% vs. 21.3%, P = .007), extracorporeal membrane oxygenation (ECMO) (11% vs. 0.9%, P = .05), and tracheostomy (22.2% vs. 3.6%, P = .01). Postoperatively, patients with pulmonary malformations more frequently required mechanical ventilation >48 hours (78% vs. 37%, P =.005) and ECMO use (11% vs. 0.9%, P = .05). Pulmonary malformation patients and children with normal anatomy did not differ in terms of postoperative tracheostomy (16.7% vs. 4.4%, P > .05), dehiscence (6% vs. 0%, P > .05%), restenosis (11% vs. 6%, P > .05) or postoperative figure 8 deformity (6% vs. 3%, P > .05). Mortality, however, was significantly increased (22.2% vs. 3.6%, P = .01) in children with pulmonary malformations. Although slide tracheoplasty can be successfully performed in patients with abnormal pulmonary anatomy, surgeons and families should anticipate a more difficult postoperative course, with possible associated prolonged mechanical ventilation, ECMO use, and higher mortality than in children with tracheal stenosis alone. 4. Laryngoscope, 127:1283-1287, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

[Characteristics of pregnancy and delivery of fetuses affected by either central nervous system malformations or chromosomal abnormalities].

PubMed

Friedler, Jordana Mashiach; Mazor, Moshe; Shoham-Vardi, Ilana; Bashiri, Asher

2011-11-01

To determine whether fetuses affected by either chromosomal abnormalities or central nervous system (CNS) malformations are prone to complications during pregnancy and delivery. In this study, 320 singleton pregnancies with CNS malformations and 133 singleton pregnancies with chromosomal abnormaLities were compared with 149,112 singleton births without any known congenital anomalies. Exclusion criteria were: births with other congenital anomalies or malformations, pregnancies Lacking prenatal care and multiple pregnancies. Data was obtained using the computerized birth discharge records. The statistical analysis was performed with the SPSS package. There were no statistically significant differences in maternal age, ethnicity, uterine anomalies or parity. The ratio of general anesthesia was almost double in the study groups compared to the control group: 25% in the CNS malformation group (RR 2.617, CI 2.031-3.372) and 25.6% in the chromosomal abnormality group (RR 2.696, CI 1.825-3.982) and 11.3% in the control group (p < 0.001). There were nearly double cesarean sections (CS) rates in both study groups: 21.5% in the CNS malformation group, 20.3% in the chromosomal abnormaLity group and 12% in the control group. A logistic regression model that included previous CS, maLpresentation, non-reassuring fetal heart monitor (NRFHR) and presence of a malformation, concluded that the presence of a malformation was not an independent risk factor for CS. However, indirect causes, such as malpresentation (4.34 OR), were independently associated with the malformations. Fetuses affected by either CNS malformations or chromosomal abnormalities have a higher rate of pregnancy and delivery complications, including those which increase the risk of maternal morbidity and mortality.

Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations.

PubMed

Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J; Seely, Ellen W; Mogun, Helen; Dejene, Sara Z; Fischer, Michael A; Friedman, Alexander M; Hernandez-Diaz, Sonia; Huybrechts, Krista F

2017-01-01

To examine the association between first-trimester angiotensin-converting enzyme (ACE) inhibitor exposure and the risk of overall major congenital, cardiac, and central nervous system malformations. We used a cohort of completed pregnancies linked to liveborn neonates derived from Medicaid claims from 2000 to 2010. We examined the risk of malformations associated with first-trimester exposure to an ACE inhibitor. Propensity score-based methods were used to control for potential confounders including maternal demographics, medical conditions, exposure to other medications, and measures of health care utilization. The cohort included 1,333,624 pregnancies, of which 4,107 (0.31%) were exposed to ACE inhibitors during the first trimester. The prevalence of overall malformations in the ACE inhibitor-exposed pregnancies was 5.9% compared with 3.3% in the unexposed (unadjusted relative risk, 1.82; 95% confidence interval [CI] 1.61-2.06), of cardiac malformations was 3.4% compared with 1.2% (relative risk 2.95, 95% CI 2.50-3.47), and of central nervous system malformations was 0.27% compared with 0.18% (relative risk 1.46, 95% CI 0.81-2.64). After restricting the cohort to pregnancies complicated by chronic hypertension (both exposed and unexposed) and accounting for other confounding factors, there was no significant increase in the risk of any of the outcomes assessed. Relative risks associated with first-trimester ACE inhibitor exposure were 0.89 (95% CI 0.75-1.06) for overall malformations, 0.95 (95% CI 0.75-1.21) for cardiac malformations, and 0.54 (95% CI 0.26-1.11) for CNS malformations. After accounting for confounders, among women with hypertension, exposure to ACE inhibitors during the first trimester was not associated with an increased risk of major congenital malformations.

Surgical management of venous malformations.

PubMed

Loose, D A

2007-01-01

Among vascular malformations, the predominantly venous malformations represent the majority of cases. They form a clinical entity and therefore need clear concepts concerning diagnosis and treatment. This paper presents an overview of contemporary classification as well as tactics and techniques of treatment. According to the Hamburg Classification, predominantly venous malformations are categorized into truncular and extratruncular forms, with truncular forms distinguished as obstructions and dilations, and extratruncular forms as limited or infiltrating. The tactics of treatment represent surgical and non-surgical methods or combined techniques. Surgical approaches utilize different tactics and techniques that are adopted based on the pathologic form and type of the malformation: (I) operation to reduce the haemodynamic activity of the malformation; (II) operation to eliminate the malformation; and (III) reconstructive operation. As for (I), a type of a tactic is the operation to derive the venous flow. In (II), the total or partial removal of the venous malformation is demonstrated subdivided into three different techniques. In this way, the infiltrating as well as the limited forms can be treated. An additional technique is dedicated to the treatment of a marginal vein. Approach (III) involves the treatment of venous aneurysms, where a variety of techniques have been successful. Long-term follow-up demonstrates positive results in 91% of the cases. Congenital predominantly venous malformations should be treated according to the principles developed during the past decades in vascular surgery, interventional treatment and multidisciplinary treatment. The days of predominantly conservative treatment should be relegated to the past. Special skills and experiences are necessary to carry out appropriate surgical strategy, and the required operative techniques should be dictated by the location and type of malformation and associated findings.

Dynamic MRI for distinguishing high-flow from low-flow peripheral vascular malformations.

PubMed

Ohgiya, Yoshimitsu; Hashimoto, Toshi; Gokan, Takehiko; Watanabe, Shouji; Kuroda, Masayoshi; Hirose, Masanori; Matsui, Seishi; Nobusawa, Hiroshi; Kitanosono, Takashi; Munechika, Hirotsugu

2005-11-01

The purpose of our study was to assess the usefulness of dynamic MRI in distinguishing high-flow vascular malformations from low-flow vascular malformations, which do not need angiography for treatment. Between September 2001 and January 2003, 16 patients who underwent conventional and dynamic MRI had peripheral vascular malformations (six high- and 10 low-flow). The temporal resolution of dynamic MRI was 5 sec. Time intervals between beginning of enhancement of an arterial branch in the vicinity of a lesion in the same slice and the onset of enhancement in the lesion were calculated. We defined these time intervals as "artery-lesion enhancement time." Time intervals between the onset of enhancement in the lesion and the time of the maximal percentage of enhancement above baseline of the lesion within 120 sec were measured. We defined these time intervals as "contrast rise time" of the lesion. Diagnosis of the peripheral vascular malformations was based on angiographic or venographic findings. The mean artery-lesion enhancement time of the high-flow vascular malformations (3.3 sec [range, 0-5 sec]) was significantly shorter than that of the low-flow vascular malformations (8.8 sec [range, 0-20 sec]) (Mann-Whitney test, p < 0.05). The mean maximal lesion enhancement time of the high-flow vascular malformations (5.8 sec [range, 5-10 sec]) was significantly shorter than that of the low-flow vascular malformations (88.4 sec [range, 50-100 sec]) (Mann-Whitney test, p < 0.01). Dynamic MRI is useful for distinguishing high-flow from low-flow vascular malformations, especially when the contrast rise time of the lesion is measured.

Transverse sinus stenosis in adult patients with Chiari malformation type I.

PubMed

Saindane, Amit M; Bruce, Beau B; Desai, Nilesh K; Roller, Lauren A; Newman, Nancy J; Biousse, Valérie

2014-10-01

Transverse sinus stenosis is an imaging finding very highly associated with elevated intracranial pressure (ICP). Patients with the Chiari I malformation may potentially have elevated ICP due to impairment of CSF flow at the foramen magnum. This study evaluated whether patients with Chiari I malformation have transverse sinus stenosis and other imaging findings indicative of elevated ICP. Thirty patients with Chiari I malformation treated surgically and 76 control subjects were identified retrospectively. All control subjects and all patients with Chiari I malformation (preoperatively) underwent standardized contrast-enhanced brain MRI including a contrast-enhanced 3D T1-weighted sequence from which curved reformats of the transverse sinuses were generated. Two different readers blinded to the diagnosis then independently evaluated these curved reformats for severity of transverse sinus stenosis. Orbital and skull-base findings previously described in association with elevated ICP were also evaluated. Frequency of MRI findings between the two groups was compared. Patients with Chiari I malformation had significantly greater frequency of unilateral or bilateral transverse sinus stenosis than did control subjects (p < 0.001). There was complete interreader agreement on presence or absence of transverse sinus stenosis by patient (κ = 1.0 [95% CI, 0.89-1.0]). Logistic regression analysis controlling for age, sex, and body mass index found that transverse sinus stenosis significantly predicted Chiari I malformation versus control status (odds ratio, 11.2 [95% CI, 2.1-59.0]; p = 0.004) but that no other features were significantly associated with the Chiari I malformation. Patients with Chiari I malformation who had transverse sinus stenosis had significantly greater pituitary flattening than did those without transverse sinus stenosis (p = 0.02). Patients with Chiari I malformation have higher likelihood of transverse sinus stenosis, which may reflect associated elevated ICP.

[Coexistence of female sexual organ malformation and urinary tract anomalies].

PubMed

Rzymski, P; Szpakowska-Rzymska, I; el Yubi, R; Wilczak, M; Sajdak, S; Opala, T

2001-02-01

The aim of the study was to estimate the correlation between sexual organs and urinary tract malformation. The retrospective analysis of clinical data obtained from 50 patients with sexual organs anomalies diagnosed in the Academic Gynaecological Centre between 1992-1999 was performed. Material included 24 patients with the Meyer-Rokitansky-Küster-Hauser syndrome and 26 with other sexual organs' malformations. Frequency of urinary tract anomalies was 42%, 11 patients with Meyer-Rokitansky-Küster-Hauser syndrome and 11 with other malformations. The gravity of urinary tract anomalies showed no statistical significant difference dependent on the type and symmetry of genital malformation. Urinary tract anomalies were more frequent in cases of asymmetric genital malformation and the difference was statistically significant. Intravenous urography proofed to be more sensitive than ultrasonography in diagnosing urinary tract anomalies.

Chronic hypertension in pregnancy and the risk of congenital malformations: a cohort study.

PubMed

Bateman, Brian T; Huybrechts, Krista F; Fischer, Michael A; Seely, Ellen W; Ecker, Jeffrey L; Oberg, Anna S; Franklin, Jessica M; Mogun, Helen; Hernandez-Diaz, Sonia

2015-03-01

Chronic hypertension is a common medical condition in pregnancy. The purpose of the study was to examine the association between maternal chronic hypertension and the risk of congenital malformations in the offspring. We defined a cohort of 878,126 completed pregnancies linked to infant medical records using the Medicaid Analytic Extract. The risk of congenital malformations was compared between normotensive controls and those with treated and untreated chronic hypertension. Confounding was addressed using propensity score matching. After matching, compared with normotensive controls, pregnancies complicated by treated chronic hypertension were at increased risk of congenital malformations (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.2-1.5), as were pregnancies with untreated chronic hypertension (OR 1.2; 95% CI, 1.1-1.3). In our analysis of organ-specific malformations, both treated and untreated chronic hypertension was associated with a significant increase in the risk of cardiac malformations (OR, 1.6; 95% CI, 1.4-1.9 and OR, 1.5; 95% CI, 1.3-1.7, respectively). These associations persisted across a range of sensitivity analyses. There is a similar increase in the risk of congenital malformations (particularly cardiac malformations) associated with treated and untreated chronic hypertension that is independent of measured confounders. Studies evaluating the teratogenic potential of antihypertensive medications must control for confounding by indication. Fetuses and neonates of mothers with chronic hypertension should be carefully evaluated for potential malformations, particularly cardiac defects. Copyright © 2015 Elsevier Inc. All rights reserved.

A developmental and genetic classification for midbrain-hindbrain malformations

PubMed Central

Millen, Kathleen J.; Dobyns, William B.

2009-01-01

Advances in neuroimaging, developmental biology and molecular genetics have increased the understanding of developmental disorders affecting the midbrain and hindbrain, both as isolated anomalies and as part of larger malformation syndromes. However, the understanding of these malformations and their relationships with other malformations, within the central nervous system and in the rest of the body, remains limited. A new classification system is proposed, based wherever possible, upon embryology and genetics. Proposed categories include: (i) malformations secondary to early anteroposterior and dorsoventral patterning defects, or to misspecification of mid-hindbrain germinal zones; (ii) malformations associated with later generalized developmental disorders that significantly affect the brainstem and cerebellum (and have a pathogenesis that is at least partly understood); (iii) localized brain malformations that significantly affect the brain stem and cerebellum (pathogenesis partly or largely understood, includes local proliferation, cell specification, migration and axonal guidance); and (iv) combined hypoplasia and atrophy of putative prenatal onset degenerative disorders. Pertinent embryology is discussed and the classification is justified. This classification will prove useful for both physicians who diagnose and treat patients with these disorders and for clinical scientists who wish to understand better the perturbations of developmental processes that produce them. Importantly, both the classification and its framework remain flexible enough to be easily modified when new embryologic processes are described or new malformations discovered. PMID:19933510

Histologic change of arteriovenous malformations of the face and scalp after free flap transfer.

PubMed

Tark, K C; Chung, S

2000-07-01

In three patients with long-standing vascular malformations of the face and scalp, radial forearm free flaps were transferred after a near-total excision of the lesion. All patients had typical high-flow malformations with thrill and bruit. The onset and progression of the malformations were analyzed through clinical and histologic studies. After free flap transfer, the vascular malformations were followed up grossly and histologically for between 4 and 9 years. There was no recurrence of arteriovenous malformation after free flap transfer. The portion of the residual lesion adjacent to the transferred free flap disappeared, and the remaining discoloration also vanished grossly. Histologic comparison of immediate postoperative and 4-month postoperative specimens from the margin and residual lesion using Victoria blue staining showed that the typical preoperative findings for arteriovenous malformation-an intermingling of thick-walled vessels with abundant elastic fibers and thin-walled vessels without elastic fibers-had undergone change, resulting in the disappearance of the thick-walled vessels and leaving only homogeneous, thin-walled vasculature. The highly vascularized free flap, which does not contain abnormal fistulas, impacted the histologic change of the arteriovenous malformation by blocking the vicious cycle of ischemia and anatomic replacement of disfigured skin and subcutaneous tissues.

Giant occipital meningocele in an 8-year-old child with Dandy-Walker malformation.

PubMed

Talamonti, Giuseppe; Picano, Marco; Debernardi, Alberto; Bolzon, Moreno; Teruzzi, Mario; D'Aliberti, Giuseppe

2011-01-01

The possibility of an association between Dandy-Walker malformation and occipital meningocele is well-known. However, just an overall number of about 40 cases have been previously reported. Giant occipital meningocele has been described only in three newborns. Incidence, pathology, clinical presentation, and proper management of this association are still poorly defined. An 8-year-old boy with Dandy-Walker malformation and giant (25 cm in diameter) occipital meningocele is presented. This boy was born without any apparent occipital mass and harbored no other significant malformations including hydrocephalus. On admission, he was neurologically intact and the giant occipital mass presented partially calcified cyst walls. Treatment consisted of the excision of the occipital malformation, cranioplasty, and cysto-peritoneal shunt. Outcome was excellent. To the best of our knowledge, among the few reported patients with Dandy-Walker malformation associated to occipital meningocele, this is the oldest one and the one with the largest occipital meningocele; he is unique with calcified walls of the occipital meningocele and the only one who survived the repair of the giant malformation. In Dandy-Walker malformation, occipital meningocele may develop and grow regardless of hydrocephalus. Giant size may be reached and the cyst may become calcified. Surgical repair may warrant favorable outcome.

Patients with lymphatic malformations who receive the immunostimulant OK-432 experience excellent long-term outcomes.

PubMed

Ghaffarpour, N; Petrini, B; Svensson, L A; Boman, K; Wester, T; Claesson, G

2015-11-01

Sclerotherapy is the primary treatment for lymphatic malformations. The aim of this study was to evaluate the long-term outcome in patients with lymphatic malformations treated with the immunostimulant OK-432 as a sclerosant. Between 1998 and 2013, we enrolled 131 of 138 eligible patients treated with OK-432 for lymphatic malformations in a retrospective study. The malformations were categorised according to the International Society for the Study of Vascular Anomalies. The outcome was assessed with a clinical examination and a questionnaire. The lymphatic malformations were localised to the head/neck (60%), the trunk (20%) and the extremities (6%) or involved with more than one region (14%). Patients with microcystic (10%), macrocystic (21%) and mixed lymphatic malformations (69%) underwent a median number of three, two and two injection treatments, respectively. The median age at the first injection was 3.4 years. Good or excellent clinical outcomes were seen in 70% of the patients. The number of injections, previous treatment and lesion localisation, but not time to follow-up and cyst size, predicted the clinical outcome. OK-432 treatment resulted in a successful outcome in 70% of patients with lymphatic malformations. The long-term outcome was comparable to the short-term outcome. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Acquired Chiari I Malformation with Syringomyelia Secondary to Colloid Cyst with Hydrocephalus-Case Report and Review of Literature.

PubMed

Thotakura, Amit Kumar; Marabathina, Nageswara R

2017-12-01

Acquired Chiari malformation and associated syringomyelia have been previously described following lumbar puncture/drainage, lumboperitoneal shunts, and spontaneous cerebrospinal fluid leakage. In addition to these etiologies, space-occupying lesions such as meningiomas, epidermoid cysts, medulloblastomas, and arachnoid cysts are rare causes of acquired Chiari malformation and syringomyelia. We report a rare case of colloid cyst with hydrocephalus causing secondary Chiari malformation with syringomyelia. A 58-year-old lady presented with neck pain and difficulty in walking and numbness of all 4 limbs of 1-year duration. Diagnostics with magnetic resonance imaging of the head and the cervical spine were done in the referring hospital. The patients was then referred with the diagnosis of colloid cyst with hydrocephalus and Chiari malformation 1 with cervicodorsal syringomyelia. She underwent colloid cyst excision through the transcallosal approach. Postoperatively the patient showed improvement in her symptomatology. Magnetic resonance imaging of the brain and cervical spine at 6 months' follow-up showed resolved Chiari malformation and resolving syrinx. Colloid cyst with hydrocephalus is a rare cause of secondary Chiari malformation with syringomyelia. Surgical management of the underlying lesion improves acquired Chiari malformation and associated syringomyelia. Copyright © 2017 Elsevier Inc. All rights reserved.

[Hemangiomas and vascular malformations of the head and neck].

PubMed

Hassmann-Poznańska, Elibieta; Kurzyna, Agnieszka

2006-01-01

This paper presents the review of current knowledge regarding vascular lesions of the head and neck. For many years the term hemangioma was used to describe all vascular lesions. Mulliken and Glowacki classified congenital vascular lesions and recognized two distinct entities, hemangiomas-vascular tumors and vascular malformations. Hemangiomas are usually not present at birth, proliferate during first year of life and then involute. They are composed of proliferating endothelial cells. Vascular malformations are always present at birth although not always apparent, increase slowly in size throughout whole life and never involute. They enlarge by hypertrophy of malformed vessels. Vascular malformations can be further subdivided according to the type of involved vessels as arterial, arteriovenous, venous, capillary or lymphatic. Accurate diagnosis of hemangiomas and vascular malformations remains a challenge for physicians. Although majority of hemangiomas are self limiting lesions some of them may develop complications such as; ulceration, airway obstruction, ophthalmic complications, psychosocial consequences. Segmental hemangiomas are associated with the risk of structural anomalies such as those that occur in PHACE syndrome. Clinical presentation and forms of treatment of various forms of vascular malformations are presented. Vascular malformations have to be treated according to their histopathology and location, as well as their hemodynamic features shown by radiological examinations.

Identification of a novel causative mutation in the ROR2 gene in a Lebanese family with a mild form of recessive Robinow syndrome.

PubMed

Mehawej, Cybel; Chouery, Eliane; Maalouf, Diane; Baujat, Geneviève; Le Merrer, Martine; Cormier-Daire, Valérie; Mégarbané, André

2012-02-01

Autosomal recessive Robinow syndrome (OMIM 268310) is a condition caused by mutations in the ROR2 gene, the receptor tyrosine kinase-like orphan receptor 2. The main characteristic features are: a face resembling that of a fetus, cleft lip and palate, mesomelic limb shortening, a micropenis in males, hydronephrosis or urinary tract infections, and skeletal and vertebral anomalies. This study reports two sisters from a consanguineous Lebanese family with an autosomal recessive Robinow syndrome. Both presented with short stature, dysmorphic facial features, and mild bone abnormalities. One of the affected girls had a malformation of her right hand: a mesoaxial polydactyly combined with a syndactyly of the 3rd and 4th fingers, and a short right 3rd metacarpal bone. Molecular analysis of the ROR2 gene revealed the presence of a previously undescribed missense mutation: p.R272C (c.814C>T), in the cysteine-rich domain of the protein. These patients are compared with other cases, and a phenotype-genotype correlation is discussed. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Perturbation of metabonome of embryo/larvae zebrafish after exposure to fipronil.

PubMed

Yan, Lu; Gong, Chenxue; Zhang, Xiaofeng; Zhang, Quan; Zhao, Meirong; Wang, Cui

2016-12-01

The escalating demand for fipronil by the increasing insects' resistance to synthetic pyrethroids placed a burden on aquatic vertebrates. Although awareness regarding the toxicity of fipronil to fish is arising, the integral alteration caused by fipronil remains unexplored. Here, we investigated on the development toxicity of fipronil and the metabolic physiology perturbation at 120h post fertilization through GC-MS metabolomics on zebrafish embryo. We observed that fipronil dose-dependently induced malformations including uninflated swim bladder and bent spine. Further, the "omic" technique hit 26 differential metabolites after exposure to fipronil and five significant signaling pathways. We speculated that changes in primary bile acid synthesis pathway and the content of saturated fatty acid in the chemical-related group indicated the liver toxicity. Pathway of Aminoacyl-tRNA biosynthesis changed by fipronil may relate to the macromolecular synthesis. Concurrently, methane metabolism pathway was also identified while the role in zebrafish needs further determination. Overall, this study revealed several new signaling pathways in fipronil-treated zebrafish embryo/larval. Copyright © 2016 Elsevier B.V. All rights reserved.

Absence of PITX3 mutation in a Tunisian family with congenital cataract and mental retardation

PubMed Central

Chograni, Manèl; Chaabouni, Myriam; Chelly, Imen; Helayem, Mohamed Bechir

2010-01-01

Purpose The PITX3 (pituitary homeobox 3) gene encodes for a homeobox bicoid-like transcription factor. When one allele is mutated, it leads to dominant cataract and anterior segment mesenchymal dysgenesis in humans. When both copies are mutated, homozygous mutation contributes to microphtalmia with brain malformations. In the current study, a family with autosomal recessive congenital cataract (ARCC) associated with mental retardation (MR) was examined to identify PITX3 mutations. Methods Sequencing of the PITX3 gene was performed on two affected and three unaffected members of the studied Tunisian family. The results were analyzed with Sequencing Analysis 5.2 and SeqScape. Results No mutation in the four exons of PITX3 was revealed. Two substitution polymorphisms, c.439C>T and c.930C>A, were detected in exons 3 and 4, respectively. These alterations did not segregate with the disease. Conclusions Although PITX3 was shown to be essential to normal embryonic eye and brain development in vertebrates, we report the absence of PITX3 mutations in a family presenting congenital cataract and mental retardation. PMID:20376326

Identification of a novel insertion mutation in FGFR3 that causes thanatophoric dysplasia type 1.

PubMed

Lindy, Amanda S; Basehore, Monica J; Munisha, Mumingjiang; Williams, Aimee Leanne; Friez, Michael J; Writzl, Karin; Willems, Patrick; Dougan, Scott T

2016-06-01

Thanatophoric dysplasia is a type of short-limbed neonatal dwarfism that is usually lethal in the perinatal period. It is characterized by short limbs, a narrow, bell-shaped thorax, macrocephaly with a prominent forehead, and flattened vertebral bodies. These malformations result from autosomal dominant mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. In this report, we describe a novel FGFR3 insertion mutation in a fetus with shortened limbs, curved femurs, and a narrow thorax. The diagnosis of thanatophoric dysplasia type 1 was suspected clinically, and FGFR3 sequencing showed a c.742_743insTGT variant, which predicts p.R248delinsLC. In vivo studies in zebrafish demonstrated that this mutation resulted in the overexpression of zebrafish Fgfr3, leading to the over-activation of downstream signaling and dorsalized embryos. To date, no insertions or deletions in FGFR3 have been reported to cause thanatophoric dysplasia types 1 or 2; therefore, this represents the first report to describe such a mutation. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Use of intermediate guide catheters as an adjunct in extracranial embolization to avoid onyx reflux into the anastomotic vasculature. A technical note.

PubMed

Puri, Ajit S; Kühn, Anna L; Hou, Samuel Y; Wakhloo, Ajay K

2014-01-01

Onyx is a non-adhesive polymer used for embolization of arteriovenous malformations and dural arteriovenous fistulas (DAVFs). The limiting factor for Onyx embolization is usually the amount of microcatheter reflux, which can be safely tolerated. The dual microcatheter technique, compliant balloon use proximally and the use of the dual lumen Scepter balloon have been described to prevent and limit proximal Onyx reflux. We describe the use the Navien 058 intermediate guide catheter to accept the Onyx reflux in its lumen and possibly also serve as a mechanical barrier to avoid reflux into the anastomotic channel connecting the occipital artery to the vertebral artery during DAVF embolization via the occipital artery. Complete embolization of the DAVF was achieved using the lumen of the Navien catheter to accept aggressive Onyx reflux. Complete cure of the DAVF was obtained with Onyx cast filling the entire venous pouch. Besides providing distal access support, intermediate guide catheters can also prevent embolic material reflux by accepting reflux into the lumen and providing a mechanical barrier.

Use of Intermediate Guide Catheters as an Adjunct in Extracranial Embolization to Avoid Onyx Reflux into the Anastomotic Vasculature

PubMed Central

Puri, Ajit S; Kühn, Anna L; Hou, Samuel Y; Wakhloo, Ajay K

2014-01-01

Summary Onyx is a non-adhesive polymer used for embolization of arteriovenous malformations and dural arteriovenous fistulas (DAVFs). The limiting factor for Onyx embolization is usually the amount of microcatheter reflux, which can be safely tolerated. The dual microcatheter technique, compliant balloon use proximally and the use of the dual lumen Scepter balloon have been described to prevent and limit proximal Onyx reflux. We describe the use the Navien 058 intermediate guide catheter to accept the Onyx reflux in its lumen and possibly also serve as a mechanical barrier to avoid reflux into the anastomotic channel connecting the occipital artery to the vertebral artery during DAVF embolization via the occipital artery. Complete embolization of the DAVF was achieved using the lumen of the Navien catheter to accept aggressive Onyx reflux. Complete cure of the DAVF was obtained with Onyx cast filling the entire venous pouch. Besides providing distal access support, intermediate guide catheters can also prevent embolic material reflux by accepting reflux into the lumen and providing a mechanical barrier. PMID:25207904

Exposure of the eggs to 17alpha-methyl testosterone reduced hatching success and growth and elicited teratogenic effects in postembryonic life stages of crayfish.

PubMed

Vogt, Günter

2007-12-30

Testosterone is regularly found in the tissues of decapod crustaceans. Although this vertebrate-type sex hormone is not the principal factor of sex differentiation in crustaceans, it was shown to be capable of acting on the reproductive organs of shrimps and crabs. In the present study I have exposed developing eggs and stage 5 juveniles of the parthenogenetic all female marbled crayfish to 17alpha-methyl testosterone in order to test whether in freshwater crayfish sex can be changed from female to male by this androgen. MT did not elicit sex change, neither when administered during embryonic development nor during juvenile stage 5, the main period of proliferation of the oocytes. However, exposure to 100 microg/L MT from 64% to 84% embryonic development resulted in prolonged embryonic development, reduced hatching success, reduced growth of the juveniles, and severe malformations of the appendages in the juveniles. The marbled crayfish is recommended to be considered for toxicity tests due to its easy culture in the laboratory and its genotypical uniformity.

Dithiocarbamates are teratogenic to developing zebrafish through inhibition of lysyl oxidase activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boxtel, Antonius L. van, E-mail: thijs.van.boxtel@ivm.vu.n; Kamstra, Jorke H.; Fluitsma, Donna M.

2010-04-15

Dithiocarbamates (DTCs) are a class of compounds that are extensively used in agriculture as pesticides. As such, humans and wildlife are undoubtedly exposed to these chemicals. Although DTCs are thought to be relatively safe due to their short half lives, it is well established that they are teratogenic to vertebrates, especially to fish. In zebrafish, these teratogenic effects are characterized by distorted notochord development and shortened anterior to posterior axis. DTCs are known copper (Cu) chelators but this does not fully explain the observed teratogenic effects. We show here that DTCs cause malformations in zebrafish that highly resemble teratogenic effectsmore » observed by direct inhibition of a group of cuproenzymes termed lysyl oxidases (LOX). Additionally, we demonstrate that partial knockdown of three LOX genes, lox, loxl1 and loxl5b, sensitizes the developing embryo to DTC exposure. Finally, we show that DTCs directly inhibit zebrafish LOX activity in an ex vivo amine oxidase assay. Taken together, these results provide the first evidence that DTC induced teratogenic effects are, at least in part, caused by direct inhibition of LOX activity.« less

A Rare Case of Pulmonary Artery Sling with the VACTERL Association in a 20-Month-Old Infant.

PubMed

Ghandi, Yazdan; Shafiee, Akbar; Sharifi, Mehrazad; Bolandnazar, Najmeh Sadat

2017-07-01

The VACTERL association, co-occurrence of vertebral, anorectal, cardiac, tracheoesophageal, genitourinary, and limb malformations, is a rare congenital anomaly. Several cardiac anomalies have been reported as a part of the VACTERL association, particularly ventricular and atrial septal defects. Pulmonary artery sling is a rare congenital abnormality in which the left pulmonary artery arises from the right pulmonary artery. This anomaly is not frequently observed in the VACTERL association and has been rarely reported. A 20-month-old girl was admitted to our hospital due to pneumonia in the right lung, which had pulmonary artery sling as a part of the VACTERL association. Barium meal X-ray showed pressure effects on the esophagus, and computed tomography angiography revealed pulmonary artery sling. Pneumonia management was done. However, the parents of our patient refused to give consent for the surgical correction of this vascular anomaly. Three months after discharge from the hospital, the patient was visited, at which time the parents again refused surgery and treatment for their daughter despite our recommendations.

A Rare Case of Pulmonary Artery Sling with the VACTERL Association in a 20-Month-Old Infant

PubMed Central

Ghandi, Yazdan; Shafiee, Akbar; Sharifi, Mehrazad; Bolandnazar, Najmeh Sadat

2017-01-01

The VACTERL association, co-occurrence of vertebral, anorectal, cardiac, tracheoesophageal, genitourinary, and limb malformations, is a rare congenital anomaly. Several cardiac anomalies have been reported as a part of the VACTERL association, particularly ventricular and atrial septal defects. Pulmonary artery sling is a rare congenital abnormality in which the left pulmonary artery arises from the right pulmonary artery. This anomaly is not frequently observed in the VACTERL association and has been rarely reported. A 20-month-old girl was admitted to our hospital due to pneumonia in the right lung, which had pulmonary artery sling as a part of the VACTERL association. Barium meal X-ray showed pressure effects on the esophagus, and computed tomography angiography revealed pulmonary artery sling. Pneumonia management was done. However, the parents of our patient refused to give consent for the surgical correction of this vascular anomaly. Three months after discharge from the hospital, the patient was visited, at which time the parents again refused surgery and treatment for their daughter despite our recommendations. PMID:29062381

[The case of completed pregnancy of the patient with Dandy-Walker malformation].

PubMed

Beliaeva, E V; Lapshina, L V; Shaposhnikova, E V; Molgachev, A A

2018-01-01

Dandy-Walker malformation is a rare disease of the central nervous system pathology (congenital malformations of the fossa cranii posterior). The key features of this syndrome are an enlargement of the fourth ventricle; complete absence of the cerebellar vermis, the posterior midline area of cerebellar cortex responsible for coordination of the axial musculature; and cyst formation near the internal base of the skull. Pregnant patients with Dandy-Walker malformation are at high risk and are managed by multidisciplinary teams including neurologists and obstetricians. We present a case report of full-term pregnancy and uncomplicated delivery in a women with Dandy-Walker malformation.

Genetics Home Reference: megalencephaly-capillary malformation syndrome

MedlinePlus

... the prognosis of a genetic condition? Genetic and Rare Diseases Information Center Frequency The prevalence of MCAP is ... Brain Malformations Health Topic: Vascular Diseases Genetic and Rare Diseases Information Center (1 link) Megalencephaly-capillary malformation syndrome ...

Linking Brain Arteriovenous Malformations With Anorectal Hemorrhoids: A Clinical and Anatomical Review

PubMed Central

Cuoco, Joshua A.; Hoehmann, Christopher L.; Hitscherich, Kyle; Zakhary, Sherry M.; Leheste, Joerg R.

2017-01-01

ABSTRACT Patients who harbor brain arteriovenous malformations are at risk for intracranial hemorrhage. These malformations are often seen in inherited vascular diseases such as hereditary hemorrhagic telangiectasia. However, malformations within the brain also sporadically occur without a hereditary‐coding component. Here, we review recent insights into the pathophysiology of arteriovenous malformations, in particular, certain signaling pathways that might underlie endothelial cell pathology. To better interpret the origins, determinants and consequences of brain arteriovenous malformations, we present a clinical case to illustrate the phenotypic landscape of the disease. We also propose that brain arteriovenous malformations might share certain signaling dimensions with those of anorectal hemorrhoids. This working hypothesis provides casual anchors from which to understand vascular diseases characterized by arteriovenous lesions with a hemorrhagic‐ or bleeding‐risk component. Anat Rec, 2017. © The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists. Anat Rec, 300:1973–1980, 2017. © 2017 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists. PMID:28696502

Patterns of anomalies of structures of the middle ear and the facial nerve as revealed in newborn temporal bones.

PubMed

Tóth, Miklós; Sirirattanapan, Jarinratn; Mann, Wolf

2013-08-01

The purpose of this study is to offer new data about facial nerve malformations in the tympanic cavity. Prospective anatomic study of newborns to demonstrate the submacroscopic anatomy of the intratympanic facial nerve and its surrounding structures by malformations. Step-by-step microdissection of 12 newborn temporal bones and histologic evaluation of 4 middle ears showing multiple malformations. Four of 12 temporal bones presented malformation in the middle ear. All 4 temporal bones showed developmental failures of the stapes, and 3 of them had malposition of the tympanic portion of the facial nerve. In 3 cases, there was an oval window atresia, and in 1 case, the rim of the oval window was not ossified and was positioned medial to the stapes. Malformation or displacement of the stapes can be an indirect sign for facial nerve malformation. The most common site for facial nerve malformation is the tympanic portion. The tympanic segment of the nerve is devoid of bony covering in association with these anomalies of the stapes.

Intracranial Hypertension in a Patient with a Chiari Malformation Accompanied by Hyperthyroidism

PubMed Central

Pang, Chang Hwan; Kim, Chi Heon; Chung, Chun Kee

2015-01-01

The Chiari malformation is an infrequently detected congenital anomaly characterized by the downward displacement of the cerebellum with a tonsillar herniation below the foramen magnum that may be accompanied by either syringomyelia or hydrocephalus. Surgery, such as foramen magnum decompression, is indicated for a symptomatic Chiari malformation, although an incidental lesion may be followed-up without further treatment. Infrequently, increased intracranial pressure emerges due to hyperthyroidism. A nineteen-year-old girl visited our outpatient clinic presented with a headache, nausea and vomiting. A brain and spinal magnetic resonance image study (MRI) indicated that the patient had a Chiari I malformation without syringomyelia or hydrocephalus. An enlarged thyroid gland was detected on a physical examination, and serum markers indicated Graves' disease. The patient started anti-hyperthyroid medical treatment. Subsequently, the headache disappeared after the medical treatment of hyperthyroidism without surgical intervention for the Chiari malformation. A symptomatic Chiari malformation is indicated for surgery, but a surgeon should investigate other potential causes of the symptoms of the Chiari malformation to avoid unnecessary surgery. PMID:26512271

Gain-of-Function Mutations in ZIC1 Are Associated with Coronal Craniosynostosis and Learning Disability.

PubMed

Twigg, Stephen R F; Forecki, Jennifer; Goos, Jacqueline A C; Richardson, Ivy C A; Hoogeboom, A Jeannette M; van den Ouweland, Ans M W; Swagemakers, Sigrid M A; Lequin, Maarten H; Van Antwerp, Daniel; McGowan, Simon J; Westbury, Isabelle; Miller, Kerry A; Wall, Steven A; van der Spek, Peter J; Mathijssen, Irene M J; Pauws, Erwin; Merzdorf, Christa S; Wilkie, Andrew O M

2015-09-03

Human ZIC1 (zinc finger protein of cerebellum 1), one of five homologs of the Drosophila pair-rule gene odd-paired, encodes a transcription factor previously implicated in vertebrate brain development. Heterozygous deletions of ZIC1 and its nearby paralog ZIC4 on chromosome 3q25.1 are associated with Dandy-Walker malformation of the cerebellum, and loss of the orthologous Zic1 gene in the mouse causes cerebellar hypoplasia and vertebral defects. We describe individuals from five families with heterozygous mutations located in the final (third) exon of ZIC1 (encoding four nonsense and one missense change) who have a distinct phenotype in which severe craniosynostosis, specifically involving the coronal sutures, and variable learning disability are the most characteristic features. The location of the nonsense mutations predicts escape of mutant ZIC1 transcripts from nonsense-mediated decay, which was confirmed in a cell line from an affected individual. Both nonsense and missense mutations are associated with altered and/or enhanced expression of a target gene, engrailed-2, in a Xenopus embryo assay. Analysis of mouse embryos revealed a localized domain of Zic1 expression at embryonic days 11.5-12.5 in a region overlapping the supraorbital regulatory center, which patterns the coronal suture. We conclude that the human mutations uncover a previously unsuspected role for Zic1 in early cranial suture development, potentially by regulating engrailed 1, which was previously shown to be critical for positioning of the murine coronal suture. The diagnosis of a ZIC1 mutation has significant implications for prognosis and we recommend genetic testing when common causes of coronal synostosis have been excluded. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Vitamin A Deficiency Induces Congenital Spinal Deformities in Rats

PubMed Central

Li, Zheng; Shen, Jianxiong; Wu, William Ka Kei; Wang, Xiaojuan; Liang, Jinqian; Qiu, Guixing; Liu, Jiaming

2012-01-01

Most cases of congenital spinal deformities were sporadic and without strong evidence of heritability. The etiology of congenital spinal deformities is still elusive and assumed to be multi-factorial. The current study seeks to elucidate the effect of maternal vitamin A deficiency and the production of congenital spinal deformities in the offsping. Thirty two female rats were randomized into two groups: control group, which was fed a normal diet; vitamin A deficient group, which were given vitamin A-deficient diet from at least 2 weeks before mating till delivery. Three random neonatal rats from each group were killed the next day of parturition. Female rats were fed an AIN-93G diet sufficient in vitamin A to feed the rest of neonates for two weeks until euthanasia. Serum levels of vitamin A were assessed in the adult and filial rats. Anteroposterior (AP) spine radiographs were obtained at week 2 after delivery to evaluate the presence of the skeletal abnormalities especially of spinal deformities. Liver and vertebral body expression of retinaldehyde dehydrogenase (RALDHs) and RARs mRNA was assessed by reverse transcription-real time PCR. VAD neonates displayed many skeletal malformations in the cervical, thoracic, the pelvic and sacral and limbs regions. The incidence of congenital scoliosis was 13.79% (8/58) in the filial rats of vitamin A deficiency group and 0% in the control group. Furthermore, vitamin A deficiency negatively regulate the liver and verterbral body mRNA levels of RALDH1, RALDH2, RALDH3, RAR-α, RAR-β and RAR-γ. Vitamin A deficiency in pregnancy may induce congenital spinal deformities in the postnatal rats. The decreases of RALDHs and RARs mRNA expression induced by vitamin A deprivation suggest that vertebral birth defects may be caused by a defect in RA signaling pathway during somitogenesis. PMID:23071590

Org-1, the Drosophila ortholog of Tbx1, is a direct activator of known identity genes during muscle specification

PubMed Central

Schaub, Christoph; Nagaso, Hideyuki; Jin, Hong; Frasch, Manfred

2012-01-01

Members of the T-Box gene family of transcription factors are important players in regulatory circuits that generate myogenic and cardiogenic lineage diversities in vertebrates. We show that during somatic myogenesis in Drosophila, the single ortholog of vertebrate Tbx1, optomotor-blind-related-gene-1 (org-1), is expressed in a small subset of muscle progenitors, founder cells and adult muscle precursors, where it overlaps with the products of the muscle identity genes ladybird (lb) and slouch (slou). In addition, org-1 is expressed in the lineage of the heart-associated alary muscles. org-1 null mutant embryos lack Lb and Slou expression within the muscle lineages that normally co-express org-1. As a consequence, the respective muscle fibers and adult muscle precursors are either severely malformed or missing, as are the alary muscles. To address the mechanisms that mediate these regulatory interactions between Org-1, Lb and Slou, we characterized distinct enhancers associated with somatic muscle expression of lb and slou. We demonstrate that these lineage- and stage-specific cis-regulatory modules (CRMs) bind Org-1 in vivo, respond to org-1 genetically and require T-box domain binding sites for their activation. In summary, we propose that org-1 is a common and direct upstream regulator of slou and lb in the developmental pathway of these two neighboring muscle lineages. Cross-repression between slou and lb and combinatorial activation of lineage-specific targets by Org-1–Slou and Org-1–Lb, respectively, then leads to the distinction between the two lineages. These findings provide new insights into the regulatory circuits that control the proper pattering of the larval somatic musculature in Drosophila. PMID:22318630